Human CRP Gene Polymorphism Influences CRP Levels: Implications for the Prediction and Pathogenesis of Coronary Heart Disease

Objective - C-reactive protein (CRP) concentrations are predictive of cardiovascular disease, and levels are heritable, in part. We identified novel polymorphisms in the CRP gene and assessed their influence on CRP level. Methods and Results - CRP was measured in 250 male army recruits before and after strenuous exercise and perioperatively in 193 coronary artery bypass graft (CABG) patients. Two novel polymorphisms were identified in the CRP gene, - 717G>A in the promoter and + 1444C>T in the 3′UTR. Among army recruits, CRP was higher in + 1444TT homozygotes than + 1444 C-allele carriers at baseline (1.04±0.38 versus 0.55±0.06, P=0.014) and at all time points after exercise (2.35±0.68 versus 1.07±0.12, 2.11±0.53 versus 0.88±0.09, and 1.77±0.44 versus 0.71±0.09, P=0.034, P=0.007, and P=0.013, at 2, 48, and 96 hours after exercise, respectively). In the CABG patients, mean CRP (mg/L) rose from 1.97±0.36 at baseline to 167.2±5.0 72 hours postoperatively. Genotype did not influence CRP at baseline; however, peak post-CABG CRP levels were higher in + 1444TT homozygotes compared with + 1444C-allele carriers (198±17 versus 164±5, P=0.03). Conclusions - The CRP gene + 1444C>T variant influences basal and stimulated CRP level. These findings have implications both for the prediction and pathogenesis of coronary heart disease.