EDCTP Alumni Network

Fostering excellence and collaboration in the next generation of researchers

Call Career Development Fellowship (CDF)
Programme EDCTP2
Start Date 2018-07-01
End Date 2021-06-30
Project Code TMA2016CDF1566
Status Active

Title

Study of Pharmacogenetics of ARVs treatment outcomes in Mali, West Africa

Host Organisation

Institution Country
Universite des Sciences des Techniques et des Technoloquies de Bamako Mali

Students Supervised

Type Name Title University Start Date End Date
PharmaD Thesis Oumar Kassogue Distribution génotypique des gènes GSTM1 et GSTT1 dans la population générale malienne USTTB 2018 2019
PharmaD Thesis Lamine Doumbia Connaissances, attitudes et pratiques des agents de la santé sur la pharmacogénétique USTTB 2019 2020

Publications

Kassogue Y, Diakite B, Kassogue O, Konate I, Tamboura K, Diarra Z, Dehbi H, Nadifi S, Traore CB, Dao S, Doumbia S, Dolo G. Genetic polymorphism of drug metabolism enzymes (GSTM1, GSTT1 and GSTP1) in the healthy Malian population. Mol Biol Rep. 2020 Jan;47(1):393-400. doi: 10.1007/s11033-019-05143-5. Epub 2019 Oct 24. PMID: 31650384.
Kassogue Y, Diakite B, Kassogue O, Konate I, Tamboura K, Diarra Z, Maiga M, Dehbi H, Nadifi S, Traore CB, Kamate B, Dao S, Doumbia S, Dolo G. Distribution of alleles, genotypes and haplotypes of the CYP2B6 (rs3745274; rs2279343) and CYP3A4 (rs2740574) genes in the Malian population: Implication for pharmacogenetics. Medicine (Baltimore). 2021 Jul 23;100(29):e26614. doi: 10.1097/MD.0000000000026614. PMCID: PMC8294905.

Current Organisation

USTTB

Current Job Title

Associate professor in Genetic and Molecular Pathology

Students Supervised

Type Name Title University Start Date End Date
Pharmacy Oumar Kassogue PharmaD USTTB 2018 2019

Education

Institution Degree Year
Faculty of Medicine and Odontostomatology of Bamako, Mali Medical Docteur
Hassan II University of sciences, Faculty of Medicine and Pharmacy of Casablanca, Morocco, Morocco PhD in Genetic and Molecular Pathology

Areas Of Specialisation

Genetic and Molecular Pathology

Publications

Authors:
Date:
2010-09-01
Journal:
Journal of medical entomology
Content:
Reduced survival and future reproduction due to of current reproduction is a trade-off known as the cost of reproduction. Surprisingly, only a few studies have assessed the cost of reproduction in arthropod disease vectors, despite its effect on longevity, and thus on vectorial capacity. We evaluated the cost of reproduction on survival of Anopheles gambiae Giles by comparing mosquitoes that were denied exposure to the other sex, hereafter named virgins, and those that were allowed exposure to the other sex and mating, hereafter named mated. Merely 6 d of exposure to females with mating activity reduced male survival from a median of 17 d in virgins to 15 d in mated, indicating that male mating cost is substantial. The increase in mortality of mated males began several days after the exposure to females ended, indicating that mating is not associated with immediate mortality risk. Notably, body size was negatively correlated with male mortality in mated males, but not in virgins. The rate of insemination declined after 4 d of exposure to females, indicating that male mating capacity is limited and further supporting the hypothesis that mating is costly for males. Consistent with previous studies, female survival on sugar alone (median=16 d) was shorter than on blood and sugar (median=19 d), regardless if she was mated or virgin. Overall, survival of mated females was lower than that of virgins on a diet of blood and sugar, but no difference was found on a diet of sugar only. However, the cost of reproduction in females remains ambiguous because the difference in survival between virgin and mated females was driven by the difference between virgin (median=19 d) and uninseminated females exposed to males (median=17 d), rather than between virgin and inseminated females (median=19 d). Accordingly, sperm and seminal fluid, egg development, and oviposition have negligible cost in terms of female survival. Only exposure to males without insemination decreased female survival. Nonetheless, if exposure to males under natural conditions is also associated with reduced survival, it might explain why females remain monogamous.
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Authors:
Date:
2013-08-09
Journal:
DNA and cell biology
Content:
The multidrug resistance gene (MDR1) plays an important role in the transport of a wide range of drugs and elimination of xenobiotics from the body. Identification of polymorphisms and haplotypes in the MDR1 gene might not only help understand pharmacokinetics and pharmacodynamics of drugs, but also can help in the prediction of drug responses, toxicity, and side effects, especially, in the era of personalized medicine. We have analyzed the genotypic and haplotypic frequencies of the three most common single-nucleotide polymorphisms in the MDR1 gene in a sample of 100 unrelated healthy Moroccan subjects by polymerase chain reaction-restrictive fragment length polymorphism. The observed genotype frequencies were 43% for 1236CC, 49% for 1236CT, and 8% for 1236TT in exon 12; 49% for 2677GG, 47% for 2677GT, and 4% for 2677TT in exon 21; 39% for 3435CC, 51% 3435CT for 3435TT, and 10% for 3435TT in exon 26, respectively. We found that all polymorphisms were in Hardy-Weinberg equilibrium. Moderate linkage disequilibrium (LD) was observed between the three polymorphisms, the strongest LD in our study has been observed between C1236T and G2677T (D'=0.76; r(2)=0.45). We identified eight haplotypes, the most frequent were 1236C-2677G-3435C (53%), 1236T-2677T-3435T (21%), and 1236C-2677G-3435T (10%), respectively. Our findings might facilitate future studies on pharmacokinetics of P-glycoprotein substrate drugs and interindividual variability to drugs in Moroccan patients.
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Date:
2020-05-05
Journal:
Scientific reports
Content:
Metabolomic studies have demonstrated the existence of biological signatures in blood of patients with arterial hypertension, but no study has hitherto reported the sexual dimorphism of these signatures. We compared the plasma metabolomic profiles of 28 individuals (13 women and 15 men) with essential arterial hypertension with those of a healthy control group (18 women and 18 men), using targeted metabolomics. Among the 188 metabolites explored, 152 were accurately measured. Supervised OPLS-DA (orthogonal partial least squares-discriminant analysis) showed good predictive performance for hypertension in both sexes (Q2cum = 0.59 in women and 0.60 in men) with low risk of overfitting (p-value-CV ANOVA = 0.004 in women and men). Seventy-five and 65 discriminant metabolites with a VIP (variable importance for the projection) greater than 1 were evidenced in women and men, respectively. Both sexes showed a considerable increase in phosphatidylcholines, a decrease in C16:0 with an increase in C28:1 lysophosphatidylcholines, an increase in sphingomyelins, as well as an increase of symmetric dimethylarginine (SDMA), acetyl-ornithine and hydroxyproline. Twenty-nine metabolites, involved in phospholipidic and cardiac remodeling, arginine/nitric oxide pathway and antihypertensive and insulin resistance mechanisms, discriminated the metabolic sexual dimorphism of hypertension. Our results highlight the importance of sexual dimorphism in arterial hypertension.
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Authors:
Date:
2014-08-05
Journal:
Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine
Content:
Multidrug resistance gene 1 (MDR1) is known for its involvement in the detoxification through the active transport of toxic compounds from diverse origins outside the cells. These compounds could cause injury to cell DNA, which might lead in cancer like chronic myeloid leukemia (CML). Individual inherited genetic differences related to polymorphism in detoxification enzymes could be an important factor not only in carcinogen metabolism but also in susceptibility of cancer. The present study aimed to investigate the association of three single nucleotide polymorphisms (SNPs) of the MDR1 gene in the susceptibility of CML. We successively have determined the genotype profiles of 1236 C>T (exon 12); 2677 G>T (exon 21), and 3435 C>T (exon 26) SNPs by PCR-RFLP in 89 patients and 99 unrelated healthy controls. Logistic regression was used to assess the effect of each SNP on the development of CML. Interestingly, in exon 12, the 1236 TT was significantly associated with the susceptibility of CML when compared to the wild type 1236 CC (OR 2.7; 95% CI 1-7.32, p = 0.041). Additionally, the recessive model 1236 TT vs. 1236 CC/CT showed a risk of 3.3 fold (p = 0.011) with CML. In exon 26, the 3435 CT genotype was associated with a reduced risk of CML (OR 0.5; 95% CI 0.3-1, p = 0.042). In exon 21, the 2677 GT genotype seems to have a protective effect (OR 0.6; 95% CI 0.32-1.1, p = 0.074). Diplolotypes analysis has demonstrated no effect in susceptibility of CML, but 1236 CT/3435 CC and 1236 CC/2677 GT were associated with a protective effect. The haplotypes analysis showed no particular trend (global association p = 0.33). Our findings demonstrate that 1236 TT in exon 12 might contribute in the susceptibility of CML, while the 3435 CT in exon 26 as well as 1236 CT/3435 CC and 1236 CC/2677 GT combinations might be protective factors.
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Authors:
Date:
2012-06-01
Journal:
The Journal of experimental biology
Content:
Malaria in Africa is vectored primarily by the Anopheles gambiae complex. Although the mechanisms of population persistence during the dry season are not yet known, targeting dry season mosquitoes could provide opportunities for vector control. In the Sahel, it appears likely that M-form A. gambiae survive by aestivation (entering a dormant state). To assess the role of eco-physiological changes associated with dry season survival, we measured body size, flight activity and metabolic rate of wild-caught mosquitoes throughout 1 year in a Sahelian locality, far from permanent water sources, and at a riparian location adjacent to the Niger River. We found significant seasonal variation in body size at both the Sahelian and riparian sites, although the magnitude of the variation was greater in the Sahel. For flight activity, significant seasonality was only observed in the Sahel, with increased flight activity in the wet season when compared with that just prior to and throughout the dry season. Whole-organism metabolic rate was affected by numerous biotic and abiotic factors, and a significant seasonal component was found at both locations. However, assay temperature accounted completely for seasonality at the riparian location, while significant seasonal variation remained after accounting for all measured variables in the Sahel. Interestingly, we did not find that mean metabolic rate was lowest during the dry season at either location, contrary to our expectation that mosquitoes would conserve energy and increase longevity by reducing metabolism during this time. These results indicate that mosquitoes may use mechanisms besides reduced metabolic rate to enable survival during the Sahelian dry season.
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Authors:
Date:
2013-11-29
Journal:
Medical oncology (Northwood, London, England)
Content:
In the spite of the impressive results achieved with imatinib in chronic myeloid leukemia (CML) patients, differences in patient's response are observed, which may be explained by interindividual genetic variability. It is known that cytochrome P450 enzymes play a major role in the metabolism of imatinib. The present study aimed to understand the functional impact of CYP2B6 15631G>T polymorphism on the response of imatinib in CML patients and its relation to CML susceptibility. We have genotyped CYP2B6 G15631T in 48 CML patients and 64 controls by PCR-RFLP. CYP2B6 15631G>T was not found to be a risk factor for CML (OR 95 % CI, 1.12, 0.6-2, p > 0.05). Hematologic response loss was higher in patients with 15631GG/TT genotype when compared with 15631GT (36.8 vs. 13.8 %; X (2) = 3.542, p = 0.063). Complete cytogenetic response was higher in 15631GG/GT genotype groups when compared with 15631TT (X (2) = 3.298, p = 0.024). Primary cytogenetic resistance was higher in patients carrying 15631GG/TT genotype when compared with 15631GT carriers (52.6 vs. 17.2 %; X (2) = 6.692, p = 0.010). Furthermore, side effects were more common for patients carrying 15631GG genotypes when compared with GT/TT carriers (36 vs. 13.8 %; X (2) = 8.3, p = 0.004). In light of our results, identification of 15631G>T polymorphism in CML patients might be helpful to predict therapeutic response to imatinib.
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Authors:
Date:
2011-07-01
Journal:
The Journal of experimental biology
Content:
In the Sahel, the Anopheles gambiae complex consists of Anopheles arabiensis and the M and S molecular forms of A. gambiae sensu stricto. However, the composition of these malaria vectors varies spatially and temporally throughout the region and is thought to be linked to environmental factors such as rainfall, larval site characteristics and duration of the dry season. To examine possible physiological divergence between these taxa, we measured metabolic rates of mosquitoes during the wet season in a Sahelian village in Mali. To our knowledge, this study provides the first measurements of metabolic rates of A. gambiae and A. arabiensis in the field. The mean metabolic rate of A. arabiensis was higher than that of M-form A. gambiae when accounting for the effects of female gonotrophic status, temperature and flight activity. However, after accounting for their difference in body size, no significant difference in metabolic rate was found between these two species (whilst all other factors were found to be significant). Thus, body size may be a key character that has diverged in response to ecological differences between these two species. Alternatively, these species may display additional differences in metabolic rate only during the dry season. Overall, our results indicate that changes in behavior and feeding activity provide an effective mechanism for mosquitoes to reduce their metabolic rate, and provide insight into the possible strategies employed by aestivating individuals during the dry season. We hypothesize that female mosquitoes switch to sugar feeding while in dormancy because of elevated metabolism associated with blood digestion.
Identifiers:
Authors:
Date:
2019-10-24
Journal:
Molecular biology reports
Content:
Glutathione S-transferase genes, known to be highly polymorphic, are implicated in the process of phase II metabolism of many substrates, including xenobiotics, anticancer and anti-infective drugs. The detoxification activity is linked to individual genetic makeup. Therefore, the identification of alleles and genotypes in these genes within a population may help to better design genetic susceptibility and pharmacogenetic studies. We performed the present study to establish the frequencies of the GSTM1, GSTT1, and GSTP1 c. 313A > G (rs1695) polymorphisms in 206 individuals of the Malian healthy population. GSTM1 and GSTT1 were genotyped by using multiplex polymerase chain reaction, whereas genotypes of GSTP1 were identified by polymerase chain reaction followed by restriction fragment length polymorphism. The frequencies of GSTM1-null and GSTT1-null genotypes were respectively 24.3 and 41.3%. The observed genotype frequencies for GSTP1 were 25.73% homozygous wild-type AA, 49.03% heterozygous AG and 25.24% homozygous mutant GG. The frequency of GSTP1-A allele was 50.24% versus 49.76% for the GSTP1-G allele. The distribution of these three genes was homogeneous between men and women (p > 0.05). We found no statistical association between the presence of a particular profile of GSTM1 or GSTT1 with the genotypes of GSTP1 (p > 0.05). Nevertheless, we noticed that the majority of the individuals harboring the GSTM1-present or the GSTT1-present harbor also the GSTP1-AG genotype. In addition, the triple genotype GSTM1-present/GSTT1-present/AG was the most frequent with 25.2%. Our findings will facilitate future studies regarding genetic associations of multifactorial diseases and pharmacogenetic, thus opening the way to personalized medicine in our population.
Identifiers:
Authors:
Date:
2012-05-17
Journal:
Journal of insect physiology
Content:
The African malaria mosquito, Anopheles gambiae, is widespread south of the Sahara including in dry savannahs and semi-arid environments where no surface water exists for several months a year. Adults of the M form of An. gambiae persist through the long dry season, when no surface waters are available, by increasing their maximal survival from 4 weeks to 7 months. Dry season diapause (aestivation) presumably underlies this extended survival. Diapause in adult insects is intrinsically linked to depressed reproduction. To determine if reproduction of the Sahelian M form is depressed during the dry season, we assessed seasonal changes in oviposition, egg batch size, and egg development, as well as insemination rate and blood feeding in wild caught mosquitoes. Results from xeric Sahelian and riparian populations were compared. Oviposition response in the Sahelian M form dropped from 70% during the wet season to 20% during the dry season while the mean egg batch size among those that laid eggs fell from 173 to 101. Correspondingly, the fraction of females that exhibited gonotrophic dissociation increased over the dry season from 5% to 45%, while a similar fraction of the population retained developed eggs despite having access to water. This depression in reproduction the Sahelian M form was not caused by a reduced insemination rate. Seasonal variation in these reproductive parameters of the riparian M form population was less extreme and the duration of reproductive depression was shorter. Blood feeding responses did not change with the season in either population. Depressed reproduction during the dry season in the Sahelian M form of An. gambiae provides additional evidence for aestivation and illuminates the physiological processes involved. The differences between the Sahelian and riparian population suggest an adaptive cline in aestivation phenotypes between populations only 130 km apart.
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Authors:
Date:
2020-01-13
Journal:
The Pan African medical journal
Content:
Introduction:Arterial hypertension is a major public health problem in sub-Saharan Africa due to its high frequency and to the cardiovascular risk that it entails. The purpose of this study was to assess the prevalence of clinical and biological risk factors of hypertension in Bamako (Mali). Methods:We conducted a case-control study, stratified in function of the sex, of 72 participants including 36 patients with hypertension and 36 controls. Twenty-two plasma biochemical parameters have been measured and analyzed using univariate and multivariate tests. Results:Hyperhomocysteinemia was found in 55.6% of women (p = 0.03) and 100% of men (p = 0.007) with hypertension. High NT-proBNP was also found in 16.7% of women (VIP > 1 in multivariate model) and of men with hypertension (p = 0.00006). A good multivariate predictive model (OPLS-DA) was only obtained in women with high blood pressure, with Q2cum = 0.73, attesting severe sexual dimorphism associated with arterial hypertension. This model involved eight parameters whose plasma concentration was modified (homocysteine, NT-proBNP, potassium, urea, blood glucose, sodium, chlorine and total proteins). Conclusion:We registered a significant association between hyperhomocysteinemia and arterial hypertension. Therefore, the assay of homocysteine associated with good management would decrease the risk of cardiovascular diseases while improving the quality of life of hypertensive patients.
Identifiers:
Authors:
Date:
2014-01-01
Journal:
Journal of medical entomology
Content:
Changes in spatial distribution of mosquitoes over time in a Sahelian village were studied to understand the sources of the mosquitoes during the dry season when no larval sites are found. At that time, the sources of Anopheles gambiae Giles may be local shelters used by aestivating mosquitoes or migrants from distant populations. The mosquito distribution was more aggregated during the dry season, when few houses had densities 7- to 24-fold higher than expected. The high-density houses during the dry season differed from those of the wet season. Most high-density houses during the dry season changed between years, yet their vicinity was rather stable. Scan statistics confirmed the presence of one or two adjacent hotspots in the dry season, usually found on one edge of the village. These hotspots shifted between the early and late dry season. During the wet season, the hotspots were relatively stable near the main larval site. The locations of the hotspots in the wet season and early and late dry season were similar between years. Season-specific, stable, and focal hotspots are inconsistent with the predictions based on the arrival of migrants from distant localities during the dry season, but are consistent with the predictions based on local shelters used by aestivating mosquitoes. Targeting hotspots in Sahelian villages for vector control may not be effective because the degree of aggregation is moderate, the hotspots are not easily predicted, and they are not the sources of the population. However, targeting the dry-season shelters may be highly cost-effective, once they can be identified and predicted.
Identifiers:
Authors:
Date:
2020-07-03
Journal:
BMC medical genetics
Content:
BACKGROUND:Breast cancer, the most common tumor in women in Mali and worldwide has been linked to several risk factors, including genetic factors, such as the PIN3 16-bp duplication polymorphism of TP53. The aim of our study was to evaluate the role of the PIN3 16-bp duplication polymorphism in the susceptibility to breast cancer in the Malian population and to perform a meta-analysis to better understand the correlation with data from other populations. METHODS:We analyzed the PIN3 16-bp duplication polymorphism in blood samples of 60 Malian women with breast cancer and 60 healthy Malian women using PCR. In addition, we performed a meta-analysis of case-control study data from international databases, including Pubmed, Harvard University Library, Genetics Medical Literature Database, Genesis Library and Web of Science. Overall, odds ratio (OR) with 95% CI from fixed and random effects models were determined. Inconsistency was used to assess heterogeneity between studies and publication bias was estimated using the funnel plot. RESULTS:In the studied Malian patients, a significant association of PIN3 16-bp duplication polymorphism with breast cancer risk was observed in dominant (A1A2 + A2A2 vs. A1A1: OR = 2.26, CI 95% = 1.08-4.73; P = 0.02) and additive (A2 vs. A1: OR = 1.87, CI 95% = 1.05-3.33; P = 0.03) models, but not in the recessive model (P = 0.38). In the meta-analysis, nineteen (19) articles were included with a total of 6018 disease cases and 4456 controls. Except for the dominant model (P = 0.15), an increased risk of breast cancer was detected with the recessive (OR = 1.46, 95% CI = 1.15-1.85; P = 0.002) and additive (OR = 1.11, 95% CI = 1.02-1.19; P = 0.01) models. CONCLUSION:The case-control study showed that PIN3 16-bp duplication polymorphism of TP53 is a significant risk factor for breast cancer in Malian women. These findings are supported by data from the meta-analysis carried out on different ethnic groups around the world.
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Date:
2015-12-12
Journal:
BMC research notes
Content:
Hypertension is a multifactorial disease caused by the interaction between genetic and environmental factors. Mutations in the methylenetetrahydrofolate reductase gene (MTHFR) have been known to be associated with the risk of cardiovascular disease as well as hypertension. This case-control study was conducted out to measure the association of the polymorphism C677T of MTHFR with the risk of hypertension.Polymerase chain reaction followed by restriction fragment analysis length was used to identify MTHFR C677T genotypes in patients 101 patients and 102 age and sex matched healthy controls. Odds ratio with 95 % confidence interval was used to assess the risk of association.The distribution of demographic and clinical features of patients showed no particular trend (p > 0.05). However, the frequency of homozygous 677T allele was higher in patients with a family history of heart disease (30.4 vs. 9 %, p = 0.031). Interestingly, the mutant 677TT genotype was significantly associated with the susceptibility of hypertension when compared to the wild type 677CC genotype (OR 5.4, CI 1.4-19.8, p = 0.008). In addition, the recessive model 677TT vs. 677CC/CT was found to be associated with the risk of hypertension (OR 5.3, CI 1.5-19.1, p = 0.005). However, the dominant model was not associated with the risk of hypertension in our cohort (OR 1.3, CI 0.7-2.2, p = 0.4).Based on our findings, the homozygous mutant for 677TT of MTHFR gene is associated with the risk of hypertension in our population. Further studies with larger sample sizes are needed to confirm the results of this study.
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Authors:
Date:
2014-06-10
Journal:
Medical oncology (Northwood, London, England)
Content:
The glutathione S-transferases (GSTs) are phase II xenobiotic metabolizing enzymes known to be involved in the detoxification of carcinogens and anticancer drugs. Individual genetic variation linked to inherited polymorphisms of GSTT1 and GSTM1 leading to a complete loss of enzyme activity could expose subjects to develop cancer or to induce drug resistance. Indeed, despite the impressive results obtained with the imatinib, some patients with chronic myeloid leukemia (CML) fail to achieve the expected results or develop resistance. The present study aimed to examine the impact of GSTT1 and GSTM1 polymorphisms on the response to imatinib in patients with CML. Multiplex polymerase chain reaction was used to detect the genotypes of GSTT1 and GSTM1 in 60 CML patients. We found that side effects were more frequent in patients carrying GSTT1 null when compared to GSTT1 present carriers (31 vs. 16.6 %; χ (2) = 6.2; p = 0.013). The loss of hematologic response was statistically greater in patients carrying the combined genotype GSTT1 present/GSTM1 present (26.3 %) when compared to GSTT1 null/GSTM1 present (12.8 %), GSTT1 present/GSTM1 null (8.3 %) and GSTT1 null/GSTM1 null (0 %), (χ (2) = 18.85; p < 0.001). The complete cytogenetic response was higher in patients harboring the GSTT1 null/GSTM1 null (75 %) compared with GSTT1 null/GSTM1 present (55.6 %), GSTT1 present/GSTM1 null (50 %) and GSTT1 present/GSTM1 present (47.8). On the other hand, the frequency of none cytogenetic responders was more common in patients carrying GSTT1 present/GSTM1 present (34.8 %) when compared to other genotype combinations (χ (2) = 20.99; p = 0.05). Moreover, the GSTT1 present/GSTM1 present appeared to be associated with a final dose of 600 or 800 mg of imatinib, but not significantly. Based on these findings, we find that the interaction between GSTT1 and GSTM1 seems to influence treatment outcome in patients with CML. Therefore, further investigations are required to confirm these results, for better genotype-phenotype correlation.
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Authors:
Date:
2017-01-01
Journal:
Middle East Journal of Cancer
Content:
Abstract Background: Acute myeloid leukemia, as most cancers, results from exposure to carcinogens and an impaired inherited individual capacity to eliminate xenobiotics. The present case-control study measures the relationship between glutathione S-transferase (GST) T1 and M1 null genotypes and the risk of acute myeloid leukemia.Methods: We identified the GSTT1 andGSTM1 genotypes by multiplex polymerase chain reaction in 129 acute myeloid leukemia patients and 129 controls.Results: Individuals that carried GSTT1 null had a risk of acute myeloid leukemia when compared to GSTT1 present carriers (OR: 2.80; 95% CI: 1.63-4.80, P=0.00036). However, GSTM1 null did not influence the risk for acute myeloid leukemia (OR: 1.20; 95% CI: 0.72-1.97, P=0.53). The combined GSTT1 null/GSTM1 present genotype showed an association with the risk for acute myeloid leukemia compared to those that carried both functional genotypes (OR: 8.85; 95% CI: 3.09-23.8, P=0.0001). The double null genotype also showed an association with the risk for acute myeloid leukemia (OR: 2.32, 95% CI: 1.15-4.66, P=0.019).Conclusion: Both GSTT1 null and GST double-null genotypes may be risk factors for acute myeloid leukemia. Further studies are needed to confirm these results.
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Date:
2019-07-13
Journal:
Current research in translational medicine
Content:
INTRODUCTION:The multidrug resistance 1 (MDR1) gene plays an important function in carcinogens detoxification and drugs metabolism. Many authors reported that MDR1 gene influences individual susceptibility to cancers. We carried out the present case-control study to investigate the impact of MDR1 gene in the predisposition to acute myeloid leukemia (AML) in a sample of Moroccan population. In addition, we performed a meta-analysis study to discuss our results and to better highlight the influence of MDR1 gene on the susceptibility of AML. METHODS:The study included 187 AML patients and 206 controls. Genomic DNA was extracted from white blood cell by salting method. Polymorphisms of G2677 T and C3435 T were genotyped by Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), using Mbo I and Ban I restriction enzymes. Statistical analysis was performed using the software SPSS (version 19.0; SPPS Inc., Chicago, IL, USA) and MedCalcv.11.6.1.0 software. RESULTS:No statistically significant differences in genotype and allelic distribution were found in G2677 T and C3435 T polymorphisms between AML cases and controls in the Moroccan population. On the other hand, we found that the age of onset of AML in patients with homozygous mutant genotype was statistically lower than in patients with either the heterozygous or wild type genotype for both polymorphisms (P = 0.006; P = 0.03). Meta-analysis showed a significant association of C3435 T, G2677 T polymorphisms on the susceptibility of AML when considering the recessive and the allelic models. CONCLUSION:Our findings showed that the G2677 T and C3435 T polymorphisms of the MDR1 gene were associated with the age at onset of AML in our population. In addition, the meta-analysis showed that these polymorphisms could play a role in susceptibility to AML.
Identifiers:
Authors:
Kassogue Y, Diakite B, Kassogue O, Konate I, Tamboura K, Diarra Z, Dehbi H, Nadifi S, Traore CB, Dao S, Doumbia S, Dolo G , Kassogue, Y., Diakite, B., Kassogue, O. et al. Genetic polymorphism of drug metabolism enzymes (GSTM1, GSTT1 and GSTP1) in the healthy Malian population. Mol Biol Rep 47, 393–400 (2020). https://doi.org/10.1007/s11033-019-05143-5
Date:
2019-10-24
Journal:
Mol Biol Rep
Content:

Glutathione S-transferase genes, known to be highly polymorphic, are implicated in the process of phase II metabolism of many substrates, including xenobiotics, anticancer and anti-infective drugs. The detoxification activity is linked to individual genetic makeup. Therefore, the identification of alleles and genotypes in these genes within a population may help to better design genetic susceptibility and pharmacogenetic studies. We performed the present study to establish the frequencies of the GSTM1, GSTT1, and GSTP1 c. 313A > G (rs1695) polymorphisms in 206 individuals of the Malian healthy population. GSTM1 and GSTT1 were genotyped by using multiplex polymerase chain reaction, whereas genotypes of GSTP1 were identified by polymerase chain reaction followed by restriction fragment length polymorphism. The frequencies of GSTM1-null and GSTT1-null genotypes were respectively 24.3 and 41.3%. The observed genotype frequencies for GSTP1 were 25.73% homozygous wild-type AA, 49.03% heterozygous AG and 25.24% homozygous mutant GG. The frequency of GSTP1-A allele was 50.24% versus 49.76% for the GSTP1-G allele. The distribution of these three genes was homogeneous between men and women (p > 0.05). We found no statistical association between the presence of a particular profile of GSTM1 or GSTT1 with the genotypes of GSTP1 (p > 0.05). Nevertheless, we noticed that the majority of the individuals harboring the GSTM1-present or the GSTT1-present harbor also the GSTP1-AG genotype. In addition, the triple genotype GSTM1-present/GSTT1-present/AG was the most frequent with 25.2%. Our findings will facilitate future studies regarding genetic associations of multifactorial diseases and pharmacogenetic, thus opening the way to personalized medicine in our population.

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Authors:
Date:
2015-10-28
Journal:
Mediators of Inflammation
Content:
Inflammatory bowel diseases (IBD) are multifactorial disorders resulting from environmental and genetic factors. Polymorphisms in MDR1 and GSTs genes might explain individual differences in susceptibility to IBD. We carried out a case-control study to examine the association of MDR1 (C1236T and C3435T), GSTT1, and GSTM1 polymorphisms with the risk of IBD. Subjects were genotyped using PCR-RFLP for MDR1 gene and multiplex PCR for GSTT1 and GSTM1. Meta-analysis was performed to test the association of variant allele carriage with IBD risk. We report that GSTT1 null genotype is significantly associated with the risk of CD (OR: 2.5, CI: 1.2-5, P = 0.013) and UC (OR: 3.5, CI: 1.5-8.5, P = 0.004) and can influence Crohn's disease behavior. The interaction between GSTT1 and GSTM1 genes showed that the combined null genotypes were associated with the risk of UC (OR: 3.1, CI: 1.1-9, P = 0.049). Furthermore, when compared to combined 1236CC/CT genotypes, the 1236TT genotype of MDR1 gene was associated with the risk of UC (OR: 3.7, CI: 1.3-10.7, P = 0.03). Meta-analysis demonstrated significantly higher frequencies of 3435T carriage in IBD patients. Our results show that GSTT1 null and MDR1 polymorphisms could play a role in susceptibility to IBD.
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Date:
2014-11-26
Journal:
Nature
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During the long Sahelian dry season, mosquito vectors of malaria are expected to perish when no larval sites are available; yet, days after the first rains, mosquitoes reappear in large numbers. How these vectors persist over the 3-6-month long dry season has not been resolved, despite extensive research for over a century. Hypotheses for vector persistence include dry-season diapause (aestivation) and long-distance migration (LDM); both are facets of vector biology that have been highly controversial owing to lack of concrete evidence. Here we show that certain species persist by a form of aestivation, while others engage in LDM. Using time-series analyses, the seasonal cycles of Anopheles coluzzii, Anopheles gambiae sensu stricto (s.s.), and Anopheles arabiensis were estimated, and their effects were found to be significant, stable and highly species-specific. Contrary to all expectations, the most complex dynamics occurred during the dry season, when the density of A. coluzzii fluctuated markedly, peaking when migration would seem highly unlikely, whereas A. gambiae s.s. was undetected. The population growth of A. coluzzii followed the first rains closely, consistent with aestivation, whereas the growth phase of both A. gambiae s.s. and A. arabiensis lagged by two months. Such a delay is incompatible with local persistence, but fits LDM. Surviving the long dry season in situ allows A. coluzzii to predominate and form the primary force of malaria transmission. Our results reveal profound ecological divergence between A. coluzzii and A. gambiae s.s., whose standing as distinct species has been challenged, and suggest that climate is one of the selective pressures that led to their speciation. Incorporating vector dormancy and LDM is key to predicting shifts in the range of malaria due to global climate change, and to the elimination of malaria from Africa.
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Date:
2015-05-01
Journal:
SpringerPlus
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Chronic myeloid leukemia (CML), as most of cancers results from a complex interaction between genetic or non genetic factors. Exposures to xenobiotics endogenous or exogenous associated with a reduced individual ability in detoxifying activity, constitutes a risk of developing cancer. It is known that polymorphism of glutathione S-transferases (GSTs) genes affects the detoxification of xenobiotics. Thus, we conducted a case-control study in which 92 patients (Mean age ± SD, 40.62 ± 12.7 years) with CML and 93 healthy unrelated controls (Mean age ± SD, 41.38 ± 13.4 years) have participated. GSTM1 and GSTT1 genotypes were determined by multiplex polymerase chain reaction. Logistic regression was used to assess the possible link between GSTM1 and GSTT1 null genotypes and CML as well as between combined genotypes and CML. GSTM1 null genotype frequency was slightly higher in patients than control (48.9% vs. 40.9%) but, it was not associated with CML (OR 95% CI, 1.4, 0.78-2.48; p = 0.271). Moreover, GSTT1 null genotype frequency showed a similar trend between patients and control (17.4% vs. 9.7%; OR 95% CI, 1.97, 0.82-4.71; p = 0.13). Surprisingly, GSTT1 null genotype was significantly associated with the risk of CML in males (OR 95% CI, 5, 1.25-20.1; p = 0.023). The combined GSTM1 present/GSTT1 null genotype was found to have a limited effect against the risk of CML (OR 95% CI, 0.3, 0.08-0.99; p = 0.049). Our findings have shown that GSTT1 null genotype might be a risk factor of CML in males. While, GSTT1 present genotype might be considered as protective against CML. However, further studies with a large sample size are needed to confirm our findings.
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Date:
2016-09-01
Journal:
BMC genetics
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Breast cancer is the most common cause of cancer death among women. Several studies have investigated the relationship between the C3435T polymorphism of ABCB1 gene and risk of breast cancer; but the results are conflicting. In the present study, we sought to assess the relationship between the C3435T polymorphism in ABCB1 gene and the risk of breast cancer in a sample of the Moroccan population.A case control study was performed on 60 breast cancer patients and 68 healthy women. The ABCB1 C3435T polymorphism was analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Furthermore, a meta-analysis including 16 studies with 6094 cases of breast cancer and 8646 controls was performed.Genotype frequencies were 50 % for CC, 33.3 % for CT and 16.7 % for TT in patients and 41.2 % for CC, 48.5 % for CT and 10.3 % for TT respectively in the control group. This difference was not statistically significant. The same trend as observed in the allele distribution between patients and controls (P = 0.84). Findings from the meta-analysis showed that the ABCB1 C3435T polymorphism was not associated with an increased risk of breast cancer in the dominant model (OR = 0.907; 95 % CI = 0.767-1.073; P = 0.25) as well as in the recessive model (OR = 1.181; 95 % CI = 0.973-1.434; P = 0.093) and in the allele contrast model (OR = 1.098; 95 % CI = 0.972-1.240; P = 0.133). However, the stratification of studies on ethnic basis showed that the TT genotype was associated with the risk of breast cancer in Asians (OR = 1.405; 95 % CI = 1.145-1.725; P = 0.001), Caucasians (OR = 1.093; 95 % CI = 1.001-1.194; P = 0.048) and North African (OR = 2.028; 95 % CI = 1.220-3.371; P = 0.006).We have noted that the implication of C3435T variant on the risk of breast cancer was ethnicity-dependent. However, there is no evidence that ABCB1 C3435T polymorphism could play a role in susceptibility to breast cancer in Morocco. Further studies with a larger sample size, extended to other polymorphisms are needed to understand the influence of ABCB1 genetic variants on the risk of breast cancer.
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Date:
2008-07-01
Journal:
Journal of medical entomology
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Mating in Anopheles gambiae has been observed only in outdoor swarms. Here we evaluate whether mating also occurs indoors. Mark-release-recapture of virgin males and females in natural houses showed that mating occurred over a single day even when mosquitoes can leave the house through exit traps and without adaptation to laboratory conditions. In these experiments, insemination rate in the M molecular form of An. gambiae (and An. arabiensis) was higher than that of the S form (15 versus 6%). Under these conditions, smaller females of the M form mated more frequently than larger females of that form. Sampling mosquitoes throughout the day showed that both sexes enter houses around sunrise and leave around sunset, staying indoors together from dawn to dusk. In an area dominated by the M form, the daily rate of insemination in samples from exit traps was approximately 5% higher than in those from entry traps, implying that mating occurred indoors. Importantly, frequency of cross mating between the molecular forms was as high as that between members of the same form, indicating that, indoors, assortative mating breaks down. Altogether, these results suggest that indoor mating is an alternative mating strategy of the M molecular form of An. gambiae. Because naturally occurring mating couples have not yet been observed indoors, this conclusion awaits validation.
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Date:
2011-06-06
Journal:
Malaria Journal
Content:
Persistence of African anophelines throughout the long dry season (4-8 months) when no surface waters are available remains one of the enduring mysteries of medical entomology. Recent studies demonstrated that aestivation (summer diapause) is one mechanism that allows the African malaria mosquito, Anopheles gambiae, to persist in the Sahel. However, migration from distant localities - where reproduction continues year-round - might also be involved.To assess the contribution of aestivating adults to the buildup of populations in the subsequent wet season, two villages subjected to weekly pyrethrum sprays throughout the dry season were compared with two nearby villages, which were only monitored. If aestivating adults are the main source of the subsequent wet-season population, then the subsequent wet-season density in the treated villages will be lower than in the control villages. Moreover, since virtually only M-form An. gambiae are found during the dry season, the reduction should be specific to the M form, whereas no such difference is predicted for S-form An. gambiae or Anopheles arabiensis. On the other hand, if migrants arriving with the first rain are the main source, no differences between treated and control villages are expected across all members of the An. gambiae complex.The wet-season density of the M form in treated villages was 30% lower than that in the control (P < 10-4, permutation test), whereas no significant differences were detected in the S form or An. arabiensis.These results support the hypothesis that the M form persist in the arid Sahel primarily by aestivation, whereas the S form and An. arabiensis rely on migration from distant locations. Implications for malaria control are discussed.
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Date:
2010-09-01
Journal:
The American journal of tropical medicine and hygiene
Content:
The African malaria mosquito, Anopheles gambiae, inhabits diverse environments including dry savannas, where surface waters required for larval development are absent for 4-8 months per year. Under such conditions, An. gambiae virtually disappears. Whether populations survive the long dry season by aestivation (a dormant state promoting extended longevity during the summer) or are reestablished by migrants from distant locations where larval sites persist has remained an enigma for over 60 years. Resolving this question is important, because fragile dry season populations may be more susceptible to control. Here, we show unequivocally that An. gambiae aestivates based on a demographic study and a mark release-recapture experiment spanning the period from the end of one wet season to the beginning of the next. During the dry season, An. gambiae was barely detectable in Sahelian villages of Mali. Five days after the first rain, before a new generation of adults could be produced, mosquito abundance surged 10-fold, implying that most mosquitoes were concealed locally until the rain. Four days after the first rain, a marked female An. gambiae s.s. was recaptured. Initially captured, marked, and released at the end of the previous wet season, she has survived the 7-month-long dry season. These results provide evidence that An. gambiae persists throughout the dry season by aestivation and open new questions for mosquito and parasite research. Improved malaria control by targeting aestivating mosquitoes using existing or novel strategies may be possible.
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