Interactions of genetic and non-genetic factors on plasma hs-CRP concentration in a Korean community-based cohort study

Abstract

High sensitivity C-reactive protein (hs-CRP) level is a predictor of cardiovascular disease. We investigated gene-environment interactions that affect hs-CRP levels in a community-based cohort. We evaluated the effects of 11 non-genetic factors on hs-CRP level in 866 Korean elderly and performed single marker analyses of 25 single-nucleotide polymorphisms (SNPs) in eight loci (i.e. IL6R, CRP, GCKR, IL6, CYP17A1, HNF1A, APOE, and 12q23.2) under each of additive, dominant, and recessive genetic model. Finally, we evaluated gene-environment interactions using generalized linear models with adjusting for age, sex, and body mass index (BMI). The general linear model identified several non-genetic risk factors associated with hs-CRP level, the most significant examples of which are high BMI (β = 0.039, P = 5.3 × 10−6), total cholesterol to HDL cholesterol ratio (T/HDL, β = 0.072, P = 2.1 × 10−4), and current smoking status (β = 0.225, P = 0.005). Single SNP analyses for seven genes revealed strong evidence for associations that affect hs-CRP levels (P = 8.9 × 10−5 to 0.032). The interactions between IL6R (rs2228145) and both high T/HDL and systolic blood pressure (P G×E = 0.009 and 0.045, respectively), CRP (rs7553007) and sleeping less than 8 hours per day (P G×E = 4.0 × 10−4), IL6 (rs2097677) and current alcohol drinking (P G×E = 0.026), and HNF1A (rs1169288) with regular exercise (P G×E = 0.035) significantly increased the hs-CRP levels in the current study. Common susceptibility variants and their interactions with non-genetic factors affect the inter-individual variability of plasma hs-CRP concentrations.