|Call||Career Development Fellowship (CDF)|
Study of Pharmacogenetics of ARVs treatment outcomes in Mali, West Africa
Main objective : To study the genetic factors that influence the response to ARV treatment in patients living with HIV. Secondary objectives - To establish the genotypic frequencies of the CYP2B6, CYP3A4, GST and MDR1 in the general population of Mali and in HIV+ patients. - To determine the influence of genotypes and haplotypes of these genes on viral load and CD4 count, - Determine the influence of genotypes and haplotypes of these genes on the concentration of concentration of ARVs - Determine the influence of genotypes and haplotypes of these genes on ARV toxicity.4 - To study the influence of these genes on the occurrence of opportunistic infections
|Universite des Sciences des Techniques et des Technoloquies de Bamako||Mali|
- Recruitment of healthy subjects It is known that the frequency of SNPs varies considerably from one population to another. Certain SNPs may be involved in the variability of responses to treatment in a population and not in another. Therefore, the interest to establish their frequencies in each population to better assess their medical implications. However, these data are missing for our population. In addition, the determination of the frequency of alleles and genotypes in the healthy population helps to target the most frequent SNPs. Their determination in a healthy population may be useful for a better orientation of the pharmacogenetic study and avoiding bias due to sample selections. In the proposed study, we will recruit after obtaining the informed consent healthy male and female adult volunteers aged between 18-75 years (age and sex matched to the HIV + patients) in Bamako from the teaching hospital of Point G (CHU Point G) where HIV+ patients will be recruited. - Recruitment of HIV+ patients Obviously, Malians patients living with HIV/AIDS have free access to ARVs. However, serious problems have been observed and recorded regarding to the patients' adherence to ARVs due mainly to side effects and toxicity. Despite the vast experience of clinicians in managing HIV+ patients, some patients fail to achieve the expected ARV treatment outcome and are then subject to several changes in the therapeutic option (ARV regimen). From the discussions with clinicians, most ignore the influence of genes on the response to ARVs. Thus, the present proposal is certainly welcomed to understand the influence of candidate genes on the responses to ARVs.
|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|
|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.|
|Kassogue Y, Diakite B, Maiga M, Kassogue O, Konate I, Tamboura K, Diarra F, Diarra Z, Sawadogo MK, Goita Y, Sissoko SB, Sissoko AS, Guirou N, Dehbi H, Nadifi S, Bah S, Traore CB, Kamate B, Dao S, Dolo G. Influence of CYP2B6 and CYP3A4 polymorphisms on the virologic and immunologic responses of patients treated with efavirenz-containing regimen. Pharmacogenet Genomics. 2022 Aug 1;32(6):219-225. doi: 10.1097/FPC.0000000000000477. Epub 2022 Jun 22. PMID: 35852913.|
Associate professor in Genetic and Molecular Pathology
|Type||Name||Title||University||Start Date||End Date|
|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|
Genetic and Molecular Pathology
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.
Objectives: The main objective of this study was to evaluate the effect of CYP2B6 and CYP3A4 polymorphisms on the virological and immunologic responses of HIV patients. A total of 153 HIV-positive patients were enlisted for the study.
Patients and methods: Viral load and median CD4 T cell counts were evaluated at baseline and month 6 (M6). Samples were identified using TaqMan genotyping assays.
Results: The AG in CYP2B6 rs2279343 was associated with VLS compared to homozygous AA. In the dominant model, the AG/GG genotypes were associated with VLS compared to the AA genotype. Moreover, in overdominant model, the AG genotype was associated with VLS compared to AA/GG. Regarding immunological response, only the AG in SNP rs2279343 CYP2B6 was associated with an increase in CD4 cell count between baseline and M6. In CYP2B6 rs3745274, the CD4 cell count at M6 was higher than that of baseline for GG carriers and for GT carriers. In CYP3A4 rs2740574, the TC carriers showed a higher median CD4 count at M6 compared to that of the baseline count, as well as for CC carriers. The best genotypes combination associated with CD4 cell count improvement were AA/AG in SNP rs2279343 and GG/GT in SNP rs3745274.
Conclusion: Our findings support the fact that CYP2B6 rs2279343 could help in the prediction of VLS and both SNPs rs3745274 and rs2279343 in CYP2B6 and CYP3A4 rs2740574 were associated with immune recovery in Malian HIV-positive patients.