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. Homozygosity for a 32-base pair (bp) deletion (Delta32) in the CCR5 gene confers resistance to HIV-1. Previous studies found an increased prevalence of hypertension among CCR5-Delta32 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-Delta32 and CCR2-64I polymorphisms by established Taqman assays.


RESULTS
The CCR5-Delta32 genotype was not found to be associated with hypertension (CCR5-Delta32 heterozygosity: odds ratio [OR] 0.99, 95% confidence interval [CI] 0.87 to 1.14; CCR5-Delta32 homozygosity: OR 1.07, 95% CI 0.68 to 1.67) among these subjects. There was also no association between CCR2-64I genotype and hypertension (CCR2-64I heterozygosity: OR 0.96, 95% CI 0.83 to 1.10; CCR2-64I homozygosity: OR 1.18, 95% CI 0.73 to 1.92). These results changed little after adjustment for potential confounding variables.


CONCLUSIONS
The results of the present study, which is much larger than previously published studies, provide no evidence that either CCR5-Delta32 or CCR2-64I is associated with hypertension.
Zhang
Mingdong
M
Viral Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH/DHHS, 6120 Executive Boulevard, Rm. 7082, MSC 7234, Rockville, MD 20852, USA.
Ardlie
Kristin
K
Wacholder
Sholom
S
Welch
Robert
R
Chanock
Stephen
S
O'Brien
Thomas R
TR
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D006973:Hypertension / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D054390:Receptors, CCR2; D019713:Receptors, CCR5 / Q000235:genetics* / Q000502:physiology; D019707:Receptors, Chemokine / Q000235:genetics* / Q000502:physiology
C515334:CCR2 protein, human; D054390:Receptors, CCR2; D019713:Receptors, CCR5; D019707:Receptors, Chemokine