Abstract 6205: Variants of CYP4V2, SERPINC1 and GP6 Are Associated with Pulmonary Embolism

Background: Pulmonary Embolism is a potentially fatal manifestation of venous thrombosis that may share genetic risk factors with deep vein thrombosis (DVT). Recently, 3 single nucleotide polymorphisms (SNPs) were reported to be associated with DVT in three studies: rs13146272 in CYP4V2 , rs2227589 in SERPINC1 , rs1613662 in GP6 . We investigated whether these 3 SNPs were also associated with pulmonary embolism. Methods: We genotyped 5840 subjects from the Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis (MEGA study). Cases were 1,206 patients who had a pulmonary embolism without a symptomatic DVT: isolated pulmonary embolism (PE iso ). Controls were 4,634 subjects who had no history of DVT or pulmonary embolism. We tested the association between genotypes and PE iso using logistic regression models that adjusted for age and sex. Results: For all three SNPs, the same allele that had been previously found to be associated with increased risk of DVT was also associated with increased risk of PE iso . For homozygous carriers of the risk allele, compared with noncarriers, the ORs were 1.34 (95% CI, 1.08–1.67) for rs13146272 in CYP4V2 , 1.85 (95% CI, 1.08–3.16) for rs2227589 in SERPINC1 , and 1.20 (95% CI, 1.04–1.39) for rs1613662 in GP6. The frequencies of risk allele homozygotes in the controls of the MEGA study were 41% for rs13146272, 1% for rs2227589, and 67% for rs1613662. Conclusions: Three SNPs previously reported to be associated with DVT were found to be associated with PE iso . Because of the high frequencies of two of these polymorphisms in Caucasians, these SNPs are likely make an appreciable contribution to the population attributable risk for PE iso .