Polymorphisms in the CC-chemokine receptor-2 (CCR2) and-5 (CCR5) genes and risk of coronary heart disease among US women

Objective: Genetic variation in CC-chemokine receptor-2 (CCR2) and -5 (CCR5),and their common haplotypes, acting through inflammatory responses, may affect atherosclerosis and risk of coronary heart disease (CHD). Method and results: We examined seven common variants in the CCR2 and CCR5 loci and risk of CHD among women in the Nurses' Health Study. During 8 years of follow-up, we documented 248 incident cases of nonfatal myocardial infarction and fatal CHD, and matched controls 2:1 based on age and smoking. The distribution of alleles was similar between cases and controls. The haplotype-specific odds ratios (ORs) were not statistically significant nor was the globally-adjusted p-value (p = 0.61). However, there was a statistically significant association for CCR5-Delta 32 and A58755G (rs2856758) between cases and controls comparing age of onset < 55 and > 55 years. For Delta 32, the OR for having the variant was 0.12 (0.02-0.76) for age < 55, and 1.14 (0.69-1.88) for age >= 55 years (p, interaction = 0.04). The CCR5-Delta 32 was in linkage disequilibriurn with 58755G, and a similar association was observed for having the 58755G. Conclusions: In this population, CCR2-CCR5 haplotypes were not associated with risk of CHD. However, our data suggest a strong inverse association for certain CCR5 variants and early age of CHD onset. (c) 2005 Elsevier Ireland Ltd. All rights reserved.