Department of Genetics, Stellenbosch University, Private Bag X1, Matieland, South Africa.
J Hum Genet. 2009 May;54(5):261-5. doi: 10.1038/jhg.2009.20. Epub 2009 Mar 13.
South Africa, like many other Southern African countries, has one of the highest HIV infection rates in the world and many individuals consequently receive antiretroviral therapy (ART). However, knowledge regarding (i) the prevalence of functional single nucleotide polymorphisms (SNPs) in pharmacologically relevant genes, and (ii) variance in pharmacotherapy both within and between different populations and ethnic groups is limited. The aim of this study was to determine whether selected polymorphisms in cytochrome P450 (CYP) genes (CYP2B6 and CYP3A4) and the multidrug-resistance 1 (ABCB1) gene underlie altered antiretroviral (ARV) drug response in two South African populations. DNA samples from 182 HIV-positive individuals of Mixed-Ancestry and Xhosa ethnicity on ART were genotyped for the A-392G SNP in CYP3A4, the G516T and A785G SNPs in CYP2B6, and the T-129C, C1236T, G2677T/A and C3435T SNPs in ABCB1. Univariate two-way analysis of variance (ANOVA) testing revealed no apparent effect of ethnicity on immune recovery (in terms of CD4-cell count) in response to ART. Univariate one-way ANOVA testing revealed a discernible effect of genotype on immune recovery in the cases of the T-129C (P=0.03) and G2677A (P<0.01) polymorphisms in the ABCB1 gene. This study serves as a basis for better understanding and possible prediction of pharmacogenetic risk profiles and drug response in individuals and ethnic groups in South Africa.
南非和许多其他南部非洲国家一样，是世界上艾滋病毒感染率最高的国家之一，因此许多人接受抗逆转录病毒治疗（ART）。然而，关于（i）在药理学相关基因中功能性单核苷酸多态性（SNP）的流行率，以及（ii）在不同人群和种族群体内部和之间药物治疗的差异的知识有限。本研究的目的是确定细胞色素 P450（CYP）基因（CYP2B6 和 CYP3A4）和多药耐药基因 1（ABCB1）中的选定 SNP 是否导致两个南非人群的抗逆转录病毒（ARV）药物反应改变。对接受 ART 的 182 名混血和科萨族 HIV 阳性个体的 DNA 样本进行 CYP3A4 的 A-392G SNP、CYP2B6 的 G516T 和 A785G SNP 以及 ABCB1 的 T-129C、C1236T、G2677T/A 和 C3435T SNP 的基因分型。单变量双向方差分析（ANOVA）测试表明，种族对免疫恢复（以 CD4 细胞计数表示）对 ART 的反应没有明显影响。单变量单向 ANOVA 测试显示，ABCB1 基因中的 T-129C（P=0.03）和 G2677A（P<0.01）多态性对免疫恢复有明显影响。本研究为更好地理解和预测南非个体和种族群体的药物遗传学风险概况和药物反应奠定了基础。
