In the HIV-1 Thai RV144 vaccine trial-the only trial to demonstrate any vaccine efficacy to date-a three-variant haplotype within the Fc gamma receptor 2C gene (FCGR2C) modified the risk of HIV-1 acquisition. A similar vaccine regimen is currently being evaluated in South Africa in the HVTN702 trial, where the predominant population is polymorphic for only a single variant in the haplotype, c.134-96C>T. To investigate the significance of c.134-96C>T in HIV-specific immunity in South Africans, this study assessed its role in HIV-1 disease progression. In a cohort of HIV-1-infected South African controllers (n = 71) and progressors (n = 73), the c.134-96C>T minor allele significantly associated with increased odds of HIV-1 disease progression (odds ratio 3.80, 95% confidence interval 1.90-7.62; P = 2.0 × 10-4, PBonf = 2.4 × 10-3). It is unlikely that the underlying mechanism involves wild-type FcγRIIc function, since only a single study participant was predicted to express wild-type FcγRIIc as determined by the FCGR2C c.798+1A>G splice-site variant. Conversely, in silico analysis revealed a potential role for c.134-96C> T in modulating mRNA transcription. In conclusion, these data provide additional evidence towards a role for FCGR2C c.134-96C>T in the context of HIV-1 and underscore the need to investigate its significance in the HVTN702 efficacy trial in South Africa.

中文翻译：

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在泰国RV144疫苗试验中，调节HIV-1感染风险的FCGR2C等位基因与HIV-1疾病进展有关。

在HIV-1泰国RV144疫苗试验中（这是迄今为止证明任何疫苗功效的唯一试验），Fcγ受体2C基因（FCGR2C）中的三变量单倍型改变了HIV-1感染的风险。南非目前正在HVTN702试验中评估类似的疫苗接种方案，该试验中的主要人群仅对单倍型c.134-96C> T的单个变异体具有多态性。为了调查c.134-96C> T在南非人的HIV特异性免疫中的重要性，本研究评估了其在HIV-1疾病进展中的作用。在一组感染了HIV-1的南非控制者（n = 71）和进展者（n = 73）中，c.134-96C> T次要等位基因与HIV-1疾病进展的几率显着相关（优势比为3.80 ，95％置信区间1.90-7.62； P = 2.0×10-4，PBonf = 2.4×10-3）。潜在的机制不太可能涉及野生型FcγRIIc功能，因为根据FCGR2C c.798 + 1A> G剪接位点变体，只有一个研究参与者被预测会表达野生型FcγRIIc。相反，计算机分析表明c.134-96C> T在调节mRNA转录中具有潜在作用。总之，这些数据为FCGR2C c.134-96C> T在HIV-1背景下的作用提供了补充证据，并强调有必要研究其在南非的HVTN702功效试验中的意义。T在调节mRNA转录中。总之，这些数据为FCGR2C c.134-96C> T在HIV-1背景下的作用提供了补充证据，并强调有必要研究其在南非的HVTN702功效试验中的意义。T在调节mRNA转录中。总之，这些数据为FCGR2C c.134-96C> T在HIV-1背景下的作用提供了补充证据，并强调有必要研究其在南非的HVTN702功效试验中的意义。