A polymorphism in the cyclooxygenase 1 gene is associated with decreased inflammatory prostaglandin F2alpha 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 F(2)(alpha) (PGF(2)(alpha)) and development of cardiovascular disease (CVD). We determined COX-1 genotypes, PGF(2)(alpha) 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 PGF(2)(alpha) (P<0.05). Two COX-1 gene variants (rs10306135 and rs883484) remained significantly associated with altered PGF(2)(alpha) formation after adjusted significance level for multiple testing (alpha-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 PGF(2)(alpha) formation and lower prevalence of CVD.
Helmersson
J
J
Centre for Research and Development, Uppsala University/County Council of Gävleborg, Sweden.
Arnlöv
J
J
Axelsson
T
T
Basu
S
S
D000368:Aged; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000235:genetics*; D051545:Cyclooxygenase 1 / Q000235:genetics*; D015237:Dinoprost / Q000235:genetics / Q000378:metabolism*; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D010641:Phenotype; D011110:Polymorphism, Genetic; D012307:Risk Factors; D013548:Sweden
D015237:Dinoprost; D051545:Cyclooxygenase 1