Influence of CYP2B6 and CYP3A4 polymorphisms on the virologic and immunologic responses of patients treated with efavirenz-containing regimen.

IF 1.7 3区 医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pharmacogenetics and genomics Pub Date : 2022-08-01 DOI:10.1097/FPC.0000000000000477
Yaya Kassogue, Brehima Diakite, Mamoudou Maiga, Oumar Kassogue, Issa Konate, Kadidiatou Tamboura, Fousseyni Diarra, Zoumana Diarra, Mahamadou Karamoko Sawadogo, Yaya Goita, Sidi Boula Sissoko, Adama Seydou Sissoko, Nouhoum Guirou, Hind Dehbi, Sellama Nadifi, Sekou Bah, Cheick Bougadari Traore, Bakarou Kamate, Sounkalo Dao, Guimogo Dolo
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Abstract

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.

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CYP2B6和CYP3A4多态性对含依非韦伦方案治疗患者病毒学和免疫反应的影响
目的:本研究的主要目的是评估CYP2B6和CYP3A4多态性对HIV患者病毒学和免疫应答的影响。共有153名hiv阳性患者参与了这项研究。患者和方法:在基线和第6个月(M6)评估病毒载量和中位CD4 T细胞计数。采用TaqMan基因分型法对样品进行鉴定。结果:与纯合子AA相比,CYP2B6 rs2279343中的AG与VLS相关。在优势模型中,与AA基因型相比,AG/GG基因型与VLS相关。此外,在过显性模型中,AG基因型与VLS的相关性高于AA/GG。在免疫应答方面,只有SNP rs2279343 CYP2B6中的AG与基线和M6之间CD4细胞计数的增加有关。在CYP2B6 rs3745274中,GG携带者和GT携带者的M6位点CD4细胞计数均高于基线。在CYP3A4 rs2740574中,TC携带者在M6处的中位CD4计数高于基线计数,CC携带者也是如此。与CD4细胞计数改善相关的最佳基因型组合是SNP rs2279343的AA/AG和SNP rs3745274的GG/GT。结论:我们的研究结果支持CYP2B6 rs2279343可以帮助预测VLS,并且CYP2B6和CYP3A4 rs2740574中的snp rs3745274和rs2279343与马里hiv阳性患者的免疫恢复相关。
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来源期刊
Pharmacogenetics and genomics
Pharmacogenetics and genomics 医学-生物工程与应用微生物
CiteScore
3.20
自引率
3.80%
发文量
47
审稿时长
3 months
期刊介绍: ​​​​Pharmacogenetics and Genomics is devoted to the rapid publication of research papers, brief review articles and short communications on genetic determinants in response to drugs and other chemicals in humans and animals. The Journal brings together papers from the entire spectrum of biomedical research and science, including biochemistry, bioinformatics, clinical pharmacology, clinical pharmacy, epidemiology, genetics, genomics, molecular biology, pharmacology, pharmaceutical sciences, and toxicology. Under a single cover, the Journal provides a forum for all aspects of the genetics and genomics of host response to exogenous chemicals: from the gene to the clinic.
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