Masebe Tracy, Bessong Pascal Obong, Ndip Roland Ndip, Meyer Debra
HIV/AIDS & Global Health Research Programme, Department of Microbiology, University of Venda, Thohoyandou 0950, South Africa.
Department of Microbiology and Parasitology, Faculty of Science, University of Buea, Buea Box 63, Cameroon.
Int J Mol Sci. 2014 Jun 26;15(7):11403-15. doi: 10.3390/ijms150711403.
Metabolic disorders and hypersensitivities affect tolerability and impact adherence to highly active antiretroviral therapy (HAART). The aim of this study was to determine the prevalence of C-482T/T-455C variants in the Apolipoprotein C3 (APOC3) promoter gene and Human leukocyte antigen (HLA)-B57:01, known to impact lipid metabolic disorders and hypersensitivity respectively; and to correlate genotypes with gender, CD4+ cell count and viral load in an HIV infected cohort in northern South Africa. Frequencies of C-482 and T-455 polymorphisms in APOC3 were determined by restriction fragment length polymorphism analysis. Allele determination for HLA-B was performed with Assign SBT software in an HLA library. Analysis of APOC3 C-482 site revealed a prevalence of 196/199 (98.5%) for CC, 1/199 (0.5%) for CT and 2/199 (1.0%) for TT genotype (p = 0.000 with 1° of freedom; χ2 = 126.551). For the T-455 site, prevalences were: 69/199 (35%) for TT and 130/199 (65%) for the CC genotype (p = 0.000 with 1° of freedom; χ2 = 199). There was no association between gender and the presence of -482 (p = 1; χ2 = 0.00001) or -455 genotypes (p = 0.1628; χ2 = 1.9842). There was no significant difference in the increase in CD4+ cell count irrespective of genotypes. Significant increases in CD4+ cell count were observed in males and females considering the -455C genotype, but not in males for the -455T genotype. Viral load decreases were significant with the -455C and -482C genotypes irrespective of gender. HLA-B57:01 was not identified in the study cohort. The apparently high prevalence of APOC3 T-455CC genotype needs confirmation with a larger samples size and triglyceride measurements to support screening of patients to pre-empt HAART associated lipid disorders.
代谢紊乱和超敏反应会影响耐受性，并对高效抗逆转录病毒疗法（HAART）的依从性产生影响。本研究的目的是确定载脂蛋白C3（APOC3）启动子基因中的C-482T/T-455C变异以及人类白细胞抗原（HLA）-B57:01的流行率，已知它们分别会影响脂质代谢紊乱和超敏反应；并在南非北部的一个HIV感染队列中，将基因型与性别、CD4+细胞计数和病毒载量进行关联分析。通过限制性片段长度多态性分析确定APOC3中C-482和T-455多态性的频率。使用Assign SBT软件在HLA文库中进行HLA-B的等位基因测定。对APOC3 C-482位点的分析显示，CC基因型的流行率为196/199（98.5%），CT基因型为1/199（0.5%），TT基因型为2/199（1.0%）（自由度为1时p = 0.000；χ2 = 126.551）。对于T-455位点，TT基因型的流行率为69/199（35%），CC基因型为130/199（65%）（自由度为1时p = 0.000；χ2 = 199）。性别与-482（p = 1；χ2 = 0.00001）或-455基因型的存在之间没有关联（p = 0.1628；χ2 = 1.9842）。无论基因型如何，CD4+细胞计数的增加均无显著差异。考虑-455C基因型时，男性和女性的CD4+细胞计数均显著增加，但对于-455T基因型，男性则不然。无论性别如何，-455C和-482C基因型的病毒载量均显著下降。在研究队列中未鉴定出HLA-B57:01。APOC3 T-455CC基因型明显较高的流行率需要通过更大样本量和甘油三酯测量来证实，以支持对患者进行筛查，从而预防与HAART相关的脂质紊乱。
