HLA-C*18:01和KIR2DL2+C1基因变异与未接受抗逆转录病毒治疗的HIV感染津巴布韦成年患者的低病毒载量相关。

HLA-C*18:01 and KIR2DL2+C1 genetic variants are associated with low viral load in cART naïve HIV-infected adult Zimbabweans.

作者信息

Mhandire Kudakwashe, Tshabalala Mqondisi, Zijenah Lynn Sodai, Mlambo Tommy, Mhandire Doreen Zvipo, Musarurwa Cuthbert, Duri Kerina, Matarira Hilda Tendisa, Dandara Collet, Rowland-Jones Sarah L, Stray-Pedersen Babill

机构信息

University of Zimbabwe College of Health Sciences, Harare, Zimbabwe.

University of Cape Town, Cape Town, South Africa.

出版信息

J Infect Dev Ctries. 2018 Dec 31;12(12):1105-1111. doi: 10.3855/jidc.10848.

DOI:10.3855/jidc.10848

PMID:32027612

Abstract

INTRODUCTION

Polymorphisms in killer cell immunoglobulin-like receptor (KIR) and human leukocyte antigen (HLA) gene families are implicated in differential outcomes of HIV infection. However, research findings on the influence of KIR and HLA-C polymorphism on HIV disease progression remain inconclusive. We thus investigated the association of KIR and HLA-C gene polymorphisms with plasma HIV load (VL) and CD4+ T lymphocyte (CD4) count in 183 chronically HIV-infected, combination antiretroviral therapy (cART) naïve Zimbabweans of Bantu origin.

METHODOLOGY

The presence or absence of 15 KIR genes were determined using sequence specific primer polymerase chain reaction while HLA-C typing was performed using chain termination DNA sequencing. Plasma VL was determined using the Cavidi Exavir viral load version 3 assay while CD4+ T lymphocytes were enumerated using flow cytometry. VLs and CD4 counts were compared between gene/genotype carriers and non-carriers using Mann-Whitney ranksum test.

RESULTS

HLA-C18:01 allele carriers had a significantly lower median log10 VL (2.87copies/mL [IQR;2.3-3.2]) than the non-C18:01 carriers (3.33copies/mL [IQR; 2.74-3.9]), p = 0.018. Further, median log10 VL was significantly lower in KIR2DL2+C1 carriers (2.745 [IQR; 2.590-2.745]) than non-KIR2DL2+C1 carriers (3.4 [IQR; 2.746-3.412]), p = 0.041. Comparison of CD4 + T lymphocyte counts between C08:02 allele carriers and non-C08:02 carriers showed a significantly higher median CD4 count in C*08:02 carriers (548cells/µL [IQR;410-684]) than in non-carriers (428cells/µL [IQR;388-537]), p = 0.034.

CONCLUSION

We conclude that the HLA-C18:01 and KIR2DL2+C1 genetic variants are associated with low VL while the C08:02 is associated with high CD4+ T lymphocyte count among cART naïve Zimbabwean adults with chronic HIV infection.

摘要

引言

杀伤细胞免疫球蛋白样受体（KIR）和人类白细胞抗原（HLA）基因家族的多态性与HIV感染的不同结果有关。然而，关于KIR和HLA - C多态性对HIV疾病进展影响的研究结果仍无定论。因此，我们调查了183名来自班图族、未经联合抗逆转录病毒治疗（cART）的慢性HIV感染津巴布韦人KIR和HLA - C基因多态性与血浆HIV载量（VL）及CD4 + T淋巴细胞（CD4）计数之间的关联。

方法

使用序列特异性引物聚合酶链反应确定15个KIR基因的有无，同时使用链终止DNA测序进行HLA - C分型。使用Cavidi Exavir病毒载量3.0版检测法测定血浆VL，使用流式细胞术计数CD4 + T淋巴细胞。使用Mann - Whitney秩和检验比较基因/基因型携带者与非携带者之间的VL和CD4计数。

结果

HLA - C18:01等位基因携带者的log10 VL中位数（2.87拷贝/毫升[四分位间距；2.3 - 3.2]）显著低于非C18:01携带者（3.33拷贝/毫升[四分位间距；2.74 - 3.9]），p = 0.018。此外，KIR2DL2 + C1携带者的log10 VL中位数（2.745[四分位间距；2.590 - 2.745]）显著低于非KIR2DL2 + C1携带者（3.4[四分位间距；2.746 - 3.412]），p = 0.041。比较C08:02等位基因携带者与非C08:02携带者之间的CD4 + T淋巴细胞计数，C*08:02携带者的CD4中位数（548个细胞/微升[四分位间距；410 - 684]）显著高于非携带者（428个细胞/微升[四分位间距；388 - 537]），p = 0.034。