Department of Anatomo-pathology, University Hospital of Point G.
Laboratory of Research and training on Molecular Pathologies, University Hospital of Point G.
Pharmacogenet Genomics. 2022 Aug 1;32(6):219-225. doi: 10.1097/FPC.0000000000000477. Epub 2022 Jun 22.
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.
Viral load and median CD4 T cell counts were evaluated at baseline and month 6 (M6). Samples were identified using TaqMan genotyping assays.
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.
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.
本研究的主要目的是评估 CYP2B6 和 CYP3A4 多态性对 HIV 患者病毒学和免疫学反应的影响。共纳入 153 例 HIV 阳性患者进行研究。
在基线和第 6 个月(M6)评估病毒载量和中位数 CD4 T 细胞计数。使用 TaqMan 基因分型检测方法鉴定样本。
与纯合 AA 相比,CYP2B6 rs2279343 的 AG 与 VLS 相关。在显性模型中,与 AA 基因型相比,AG/GG 基因型与 VLS 相关。此外,在超显性模型中,AG 基因型与 VLS 相关,与 AA/GG 相比。关于免疫反应,仅 SNP rs2279343 CYP2B6 的 AG 与基线至 M6 之间 CD4 细胞计数增加相关。在 CYP2B6 rs3745274 中,GG 携带者和 GT 携带者在 M6 时的 CD4 细胞计数高于基线时的 CD4 细胞计数。在 CYP3A4 rs2740574 中,TC 携带者在 M6 时的中位 CD4 计数高于基线时的 CD4 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。
我们的研究结果支持 CYP2B6 rs2279343 有助于预测 VLS 的事实,CYP2B6 中的 SNPs rs3745274 和 rs2279343 以及 CYP3A4 rs2740574 与马里 HIV 阳性患者的免疫恢复相关。