The genetic associations and epistatic effects of the CCR5 promoter and CCR2-V64I polymorphisms on susceptibility to HIV-1 infection in a Northern Han Chinese population.
The outcome of human immunodeficiency virus (HIV)-1 infection and course to AIDS are variable among individuals. Both chemokine receptor 5 (CCR5) and CCR2 gene polymorphisms play essential roles in the susceptibility of HIV-1 infection. To investigate the main and epistatic effects of the CCR5 promoter and CCR2-V64I polymorphisms on HIV-1 infection in the Northern Han Chinese, subjects of 91 HIV-1-infected patients and 91 health controls were recruited. Single-nucleotide polymorphisms (SNPs) in the CCR5 promoter region and CCR2-V64I variants were genotyped. In the single-locus analysis, CCR5 58755-G and CCR5 59653-T alleles were significantly associated with HIV-1 infection (odds ratio [OR]=0.529, 95% confidence interval [CI]: 0.295-0.948; OR=1.710, 95% CI: 1.039-2.814). After adjustment with age and gender, subjects with the CCR5 59653-CT genotype showed the increased risk of HIV-1 infection compared with those with the wild-type CC genotype (adjusted OR=2.502; 95% CI: 1.332-4.698). No positive association was observed in other SNPs. Haplotype-based association analysis revealed that the haplotype TATGC was associated with the susceptibility to HIV-1 infection (p=0.003). Besides, we found the significant epistatic effects between the CCR5 58755-A/G and CCR5 59029-A/G polymorphisms associated with the lower risk of HIV-1 infection. In addition, we also identified the best three-factor interaction model, including the CCR5 58755-A/G, 59029-A/G, and CCR2-V64I polymorphisms, indicating that there were also strong gene-gene interactions between the CCR5 promoter and CCR2 polymorphisms on the susceptibility of HIV-1 infection. These findings contribute to understanding the genetic mechanism for the susceptibility of HIV-1 infection in Northern Han Chinese.
School of Public Health and Family Medicine, Capital Medical University, Beijing, China.
Jiapeng
J
Lu
Aijuan
A
Sheng
Youxin
Y
Wang
Ling
L
Zhang
Jingjing
J
Wu
Manshu
M
Song
Yan
Y
He
Xinwei
X
Yu
Feifei
F
Zhao
Yezhou
Y
Liu
Shuang
S
Shao
Jie
J
Lan
Hao
H
Wu
Wei
W
Wang
D000328:Adult; D044466:Asian People; D004843:Epistasis, Genetic; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015658:HIV Infections / Q000208:ethnology / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D054390:Receptors, CCR2 / Q000235:genetics*; D019713:Receptors, CCR5 / Q000235:genetics*
C515334:CCR2 protein, human; D054390:Receptors, CCR2; D019713:Receptors, CCR5