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

Ulla Vogel, S. Segel, Claus Dethlefsen, A. Tjønneland, Anne Thoustrup Saber, Håkan Wallin, Majken Karoline Jensen, Erik Berg Schmidt, Pall Skytt Andersen, Kim Overvad

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

    Abstract

    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.

    OriginalsprogEngelsk
    TidsskriftAtherosclerosis
    Vol/bind209
    Udgave nummer1
    Sider (fra-til)155-162
    ISSN0021-9150
    DOI
    StatusUdgivet - 2010

    Citer dette

    Vogel, U., Segel, S., Dethlefsen, C., Tjønneland, A., Saber, A. T., Wallin, H., Jensen, M. K., Schmidt, E. B., Andersen, P. S., & Overvad, K. (2010). Associations between COX-2 polymorphisms, blood cholesterol and risk of acute coronary syndrome. Atherosclerosis, 209(1), 155-162. https://doi.org/doi:10.1016/j.atherosclerosis.2009.08.036