"The Genetic Associations and Epistatic Effects of the CCR5 Promoter an" by Jiapeng Lu, Aijuan Sheng et al.
 

Document Type

Journal Article

Publisher

Mary Ann Liebert

Faculty

Faculty of Computing, Health and Science

School

School of Medical Sciences / Systems and Intervention Research Centre for Health

RAS ID

14447

Comments

This is an Author's Accepted Manuscript of: Lu, J., Sheng, A., Wang, Y., Zhang, L., Wu, J., Song, M., He, Y., Yu, X., Zhao, F., Liu, Y., Shao, S., Lan, J., Wu, H., & Wang, W. (2012). 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. Genetic Testing and Molecular Biomarkers, 16(12), 1369-1375. Available here

Abstract

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.

DOI

10.1089/gtmb.2012.0235

Access Rights

free_to_read

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