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.