The CCR5-Delta32 Genetic Polymorphism and HIV-1 Infection Susceptibility: a Meta-analysis.

Jun Ni,Sheng Wang,Dan Wang

doi:10.1515/med-2018-0062

Abstract

The CC chemokine receptor 5 (CCR5) is a chemokine receptor which is widely expressed in several immune cells involved in the inflammatory responses. Previous published studies revealed the relation of the CCR5 gene (CCR5-delta32) with the risk of HIV-1 infection, but the results are debatable and inconclusive. Here by meta-analysis, we have systematically evaluated the relation between the CCR5-delta32 polymorphism and the risk of HIV-1 infection. A comprehensive search in PubMed, EMBASE, CNKI, Cochrane Library, and WanFang database was performed up to April 15, 2018. The pooled odds ratio (ORs) along with its 95% credible interval (95%CI) was used to evaluate the relation between the CCR5-delta32 polymorphism and HIV-1 infection risk. The study included 24 case-control studies involving 4,786 HIV-1 infection patients and 6,283 controls. Compared with the wild-type homozygous genotypes, the results showed that the CCR5-delta32 heterozygotes (OR=1.16, 95%CI=1.02-1.32) had an increased susceptibility to HIV-1 and the delta32 homozygous (OR=0.25, 95%CI=0.09-0.68) had significantly reduced the susceptibility to HIV-1 for healthy controls. Moreover, we have found the delta32 allele carriers (OR=0.71, 95%CI=0.54-0.94) had significantly cut down the HIV-1 infection susceptibility when using exposed uninfected (EU) as controls. We also conducted the stratified analysis by ethnicity, and there significant association was detected in Caucasian in delta32 allele carrier genotype. To summarize, our meta-analysis suggests that the CCR5-delta32 homozygous genotype (delta32/delta32) confer possible protection against HIV-1, especially the exposed uninfected groups.

Highlights

Human Immunodeficiency Virus-1 (HIV-1)/Acquired Immunodeficiency Syndrome (AIDS), the world major infectious killer remains one of the most important public health challenges in the world
Articles must satisfy the following criteria: (a) evaluated the relation between chemokine receptor 5 (CCR5)-delta32 and the risk of HIV-1 infection; (b) case-control studies on human beings, no language restriction was applied; (c) sufficient data to evaluate the odds ratios (ORs) and 95% credible interval (CI), and P values; and (e) genotype distribution in controls must be in Hardy-Weinberg equilibrium (HWE) (P < 0.001)
We found the risk of HIV-1 infection was significantly reduced in the delta32 homozygous genotype (OR=0.25, 95% credible interval (95%CI)=0.09-0.68, P=0.006) for healthy

Summary

Introduction

Human Immunodeficiency Virus-1 (HIV-1)/Acquired Immunodeficiency Syndrome (AIDS), the world major infectious killer remains one of the most important public health challenges in the world. HIV prevalence can be considered as the greatest issue in contemporary society, including economic and health crisis [1]. Many basic questions about the HIV-1 infection pathogenesis have not been answered. Several studies demonstrated that they have a significant difference in susceptibility and progression of HIV-1 infection [2,3,4]. Host genetic diversity has an important role in either disease susceptibility or resistance [4, 5]. The positive role of different genes in HIV/ AIDS progression has still remained controversial [6, 7]

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