Genetic variations in CC chemokine receptors and hypertension

Background: CC-chemokine receptor 5 (CCR5) is a co-receptor for human immunodeficiency virus type 1 (HIV-1) infection. Homozycrosity for a 32-base pair (bp) deletion (Delta 32) in the CCR5 gene confers resistance to HIV-1. Previous studies found an increased prevalence of hypertension among CCR5-Delta 32 homozygotes and among carriers of a polymorphism (CCR2-64I) found on the gene that codes a closely related chemokine receptor. The present study was carried out to verify these associations. Methods: Subjects in this cross-sectional study were selected from the Global Repository at Genomics Collaborative, which includes patients and healthy control subjects enrolled at multiple clinical sites in the United States and other nations. The current study includes 2842 subjects with hypertension and 2893 nonhypertensive control subjects from white populations in the United States and Poland. Case and control subjects were frequency matched by age, gender, and birthplace. All subjects were genotyped for CCR5-Delta 32 and CCR2-641 polymorphisms by established Taqman assays. Results: The CCR5-Delta 32 genotype was not found to be associated with hypertension (CCR5-A32 heterozygosity: odds ratio [OR] 0.99, 95% confidence interval [CI] 0.87 to 1.14; CCR5-Delta 32 homozygosity: OR 1.07, 95% CI 0.68 to 1.67) among these subjects. There was also no association between CCR2-641 genotype and hypertension (CCR2-64I heterozygosity: OR 0.96 95% CI 0.83 to 1.10: CCR2-641 homozygosity: OR 1.18, 95% CI 0.73 to 1.92). These results changed little after adjustment for potential confounding variables. Conclusion: The results of the present study, which is much larger than previously published studies, provide no evidence that either CCR5-Delta 32 or CCR2-641 is associated with hypertension.

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