Associations between COX-2 polymorphisms, blood cholesterol and risk of acute coronary syndrome

BACKGROUND: The use of specific COX-2 inhibitors in cancer prevention has been associated with higher risk of acute coronary syndrome (ACS) and myocardial infarction. The aim of this study was to investigate if the polymorphisms COX2 T8473C (rs5275), and COX2 A-1195G (rs689466), which modify the enzyme levels of COX-2, were associated with risk of ACS and if alcohol intake, smoking, and use of NSAID would modify the associations. We also wanted to investigate associations with blood lipid levels. METHODS: A case-cohort study including 1031 ACS cases and a sub-cohort of 1703 persons was nested within the population-based prospective study Diet, Cancer and Health of 57,053 individuals aged 55-64 at recruitment 1993-1997. RESULTS: Male variant allele carriers of COX-2 T8473C were at lower risk of ACS (IRR=0.75, CI=0.61-0.93, p=0.008) than homozygous wildtype carriers. There were no statistically significant interactions between genotypes and alcohol intake, smoking and NSAID use in relation to risk of ACS. Among males, there was interaction between COX-2 T8473C and alcohol in relation to total cholesterol, non-HDL cholesterol and LDL levels (p for interaction: 0.003, 0.007 and 0.01, respectively), such that variant allele carriers with low alcohol intake had the lowest lipid levels. No statistically significant associations were observed in females. CONCLUSION: This study suggests that genetically determined COX-2 levels are associated with risk of ACS and blood lipid levels among males. No consistent associations were found for females.