C-reactive protein gene polymorphisms and the risk of venous thromboembolism: a haplotype-based analysis.

C-reactive protein (CRP) is a risk predictor for future athero-thrombotic events, and its plasma concentration has a heritable component. CRP has also been suggested to play a role in the pathophysiology of venous thromboembolism. To date, no genetic-epidemiological data are available on the relation of CRP gene variants with the risk of venous thromboembolism. The present study was carried out to investigate the possible association of two previously characterized (an exonic 1059G-->C, and an intronic T-->A) CRP gene polymorphisms in a prospective, matched case-control sample from the Physicians Health Study. Allele, genotype, and haplotype distributions were similar between 130 cases and 130 matched controls. Genotype distributions were in Hardy-Weinberg equilibrium. Further investigation using a haplotype-based matched logistic regression analysis, adjusting for age, smoking, randomized treatment group (likelihood ratio test: X(2)2df = 0.19, P = 0.91) or with further controlling for body mass index, hypertension, and diabetes (likelihood ratio test: X(2)2df = 0.66, P = 0.72) yielded similar null findings. In conclusion, we found no evidence for an association between the CRP polymorphisms/haplotypes tested and the risk of venous thromboembolism.