HCP5、HLA - C和ZNRD1基因多态性对HIV病毒载量的影响。

Impact of polymorphisms in the HCP5 and HLA-C, and ZNRD1 genes on HIV viral load.

作者信息

Thørner Lise Wegner, Erikstrup Christian, Harritshøj Lene Holm, Larsen Margit Hørup, Kronborg Gitte, Pedersen Court, Larsen Carsten Schade, Pedersen Gitte, Gerstoft Jan, Obel Niels, Ullum Henrik

机构信息

Dept. of Clinical Immunology, Copenhagen University Hospital, Copenhagen, Denmark.

Dept. of Clinical Immunology, Aarhus University Hospital, Skejby, Aarhus, Denmark.

出版信息

Infect Genet Evol. 2016 Jul;41:185-190. doi: 10.1016/j.meegid.2016.03.037. Epub 2016 Apr 12.

DOI:10.1016/j.meegid.2016.03.037

PMID:27083073

Abstract

AIMS

Single nucleotide polymorphisms (SNPs) in the human leucocyte antigen (HLA) complex P5 (HCP5), HLA-C, and near the zinc ribbon domain containing 1 (ZNRD1) have been shown to influence viral load (VL) set point in HIV-infected individuals with a known seroconversion onset. We aimed to determine the influence of HCP5 rs2395029, HLA-C rs9264942, and ZNRD1 rs3869068 on VL in antiretroviral-naïve individuals and on time to the first VL<51 copies/ml and on CD4(+) T-cell recovery after initiation of combination antiretroviral therapy (cART).

MATERIAL AND METHODS

We genotyped the rs2395029 (A>C), rs9264942 (T>C), and rs3869068 (C>T) SNPs in 1897 Caucasians from The Danish HIV Cohort Study - a prospective, nationwide, population-based study of HIV-infected individuals in Denmark. General linear models evaluated the effect of SNPs on VL in antiretroviral-naïve individuals 0-18months after diagnosis and on CD4(+) T-cell recovery during cART. Cox proportional hazard regression analysis assessed the association with time to first VL<51 copies/ml. All models were assuming additive genetic effects.

RESULTS

The rs2395029, rs9264942, and rs3869068 minor alleles were associated with lower VL in antiretroviral-naïve individuals (rs2395029: [mean VL (copies/ml)], A/A: 70,795 [61,660-79,433], A/C: 33,884 [19,498-58,884], P=0.002; rs9264942: TT: 81,283 [67,608-97,724], T/C: 63,096 [54,954-75,858], CC: 38,905 [25,119-58,884], P<0.0001; rs3869068, CC: 72,444 [63,096-83,176], C/T: 45,709 [33,113-64,565], TT: 58,884 [20,417-169,824], P=0.01). Moreover, the C-alleles of rs2395029 and rs9264942 were associated with shorter time to VL<51 copies/ml: (HR [95% confidence interval], 1.67 [1.09-1.72], P=0.008; 1.16 [1.06-1.28], P=0.002; 1.30 [1.08-1.53], P=0.005, respectively, adjusted for last VL before cART). None of the SNPs predicted CD4(+) T-cell recovery during cART.

CONCLUSIONS

The minor alleles of rs2395029, rs9264942, and rs3689068 associate with lower VL among antiretroviral-naïve individuals and with shorter time to first VL<51copies/ml during cART even after adjustment for VL before cART.

摘要

目的

人类白细胞抗原（HLA）复合体P5（HCP5）、HLA - C以及含锌带结构域1（ZNRD1）附近的单核苷酸多态性（SNP）已被证明会影响已知血清转化发病时间的HIV感染者的病毒载量（VL）设定点。我们旨在确定HCP5 rs2395029、HLA - C rs9264942和ZNRD1 rs3869068对初治抗逆转录病毒治疗个体的VL、首次VL<51拷贝/ml的时间以及联合抗逆转录病毒治疗（cART）开始后CD4(+) T细胞恢复的影响。

材料与方法

我们对来自丹麦HIV队列研究的1897名白种人进行了rs2395029（A>C）、rs9264942（T>C）和rs3869068（C>T）SNP基因分型，该研究是一项针对丹麦HIV感染者的前瞻性、全国性、基于人群的研究。通用线性模型评估了SNP对诊断后0 - 18个月初治抗逆转录病毒治疗个体的VL以及cART期间CD4(+) T细胞恢复的影响。Cox比例风险回归分析评估了与首次VL<51拷贝/ml时间的关联。所有模型均假设为加性遗传效应。

结果

rs2395029、rs9264942和rs3869068的次要等位基因与初治抗逆转录病毒治疗个体较低的VL相关（rs2395029：[平均VL（拷贝/ml）]，A/A：70,795 [61,660 - 79,433]，A/C：33,884 [19,498 - 58,884]，P = 0.002；rs9264942：TT：81,283 [67,608 - 97,724]，T/C：63,096 [54,954 - 75,858]，CC：38,905 [25,119 - 58,884]，P<0.0001；rs3869068，CC：72,444 [63,096 - 83,176]，C/T：45,709 [33,113 - 64,565]，TT：58,884 [20,417 - 169,824]，P = 0.01）。此外，rs2395029和rs9264942的C等位基因与VL<51拷贝/ml的时间缩短相关：（风险比[95%置信区间]，1.67 [1.09 - 1.72]，P = 0.008；1.16 [1.06 - 1.28]，P = 0.002；1.30 [1.08 - 1.53]，P = 0.005，分别针对cART前的最后一次VL进行调整）。没有一个SNP能预测cART期间CD4(+) T细胞的恢复情况。