The Genetic Associations and Epistatic Effects of theCCR5Promoter andCCR2-V64I Polymorphisms on Susceptibility to HIV-1 Infection in a Northern Han Chinese Population
Copyright policy )The Genetic Associations and Epistatic Effects of theCCR5Promoter andCCR2-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.
- University of Chinese Academy of Sciences China (People's Republic of)
- Second Artillery General Hospital of Chinese People's Liberation Army China (People's Republic of)
- Capital Medical University China (People's Republic of)
- Edith Cowan University Australia
Male, haplotype, chemokine receptor CCR5, genetic association, chemokine receptor CCR2, genotype, isoleucine, Human immunodeficiency virus 1, HIV Infections, genetic analysis, Western blotting, Gene Frequency, valine, single nucleotide polymorphism, genetic variability, Medicine and Health Sciences, Promoter Regions, Genetic, cysteine, adult, allele, article, Human immunodeficiency virus infected patient, protein function, Middle Aged, female, risk factor, protein protein interaction, Female, wild type, alanine, amino acid substitution, Adult, gene locus, Genotype, Receptors, CCR5, Receptors, CCR2, gene frequency, Polymorphism, Single Nucleotide, promoter region, male, Asian People, 616, Humans, controlled study, Genetic Predisposition to Disease, diagnostic test accuracy study, human, genetic epistasis, Genetic Association Studies, Chinese, disease predisposition, nucleotide sequence, Epistasis, Genetic, Human immunodeficiency virus 1 infection, major clinical study, threonine, Haplotypes, gene expression, HIV-1, glycine, genetic susceptibility
Male, haplotype, chemokine receptor CCR5, genetic association, chemokine receptor CCR2, genotype, isoleucine, Human immunodeficiency virus 1, HIV Infections, genetic analysis, Western blotting, Gene Frequency, valine, single nucleotide polymorphism, genetic variability, Medicine and Health Sciences, Promoter Regions, Genetic, cysteine, adult, allele, article, Human immunodeficiency virus infected patient, protein function, Middle Aged, female, risk factor, protein protein interaction, Female, wild type, alanine, amino acid substitution, Adult, gene locus, Genotype, Receptors, CCR5, Receptors, CCR2, gene frequency, Polymorphism, Single Nucleotide, promoter region, male, Asian People, 616, Humans, controlled study, Genetic Predisposition to Disease, diagnostic test accuracy study, human, genetic epistasis, Genetic Association Studies, Chinese, disease predisposition, nucleotide sequence, Epistasis, Genetic, Human immunodeficiency virus 1 infection, major clinical study, threonine, Haplotypes, gene expression, HIV-1, glycine, genetic susceptibility
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