A polymorphism in the cyclooxygenase 1 gene is associated with decreased inflammatory prostaglandin F2α formation and lower risk of cardiovascular disease

This study investigates the impact of genetic variation in the cyclooxygenase-1 (COX-1) gene on formation of the vasoconstrictive, pro-inflammatory prostaglandin F2α (PGF2α) and development of cardiovascular disease (CVD). We determined COX-1 genotypes, PGF2α formation and CVD prevalence in a Swedish cohort of 809 men at age 77 years. Of these, 237 had a history of CVD according to the registry data. Four of nine COX-1 single nucleotide polymorphisms were associated with altered formation of PGF2α (P<0.05). Two COX-1 gene variants (rs10306135 and rs883484) remained significantly associated with altered PGF2α formation after adjusted significance level for multiple testing (α-level=0.0059). Furthermore, individuals homozygote for the variant allele rs10306135 had lower prevalence of CVD, compared to the common allele (0% versus 30%, P=0.0047). In conclusion, subjects homozygote for the variant allele of a COX-1 gene polymorphism represent a subpopulation of men with decreased PGF2α formation and lower prevalence of CVD.