Promotor polymorphisms in leukotriene C4 synthase and risk of ischemic cerebrovascular disease.

J.J. Freiberg, A. Tybjaerg-Hansen, H. Sillesen, Gorm Boje Jensen, Børge Nordestgaard, Jacob J Freiberg, Anne Tybjærg-Hansen, Henrik Sillesen, Gorm B Jensen, Børge G Nordestgaard

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    Abstract

    OBJECTIVE: Cysteinyl leukotrienes are involved in inflammation and possibly in early carotid atherosclerosis. We tested the hypothesis that the -444 A/C and -1072 G/A polymorphisms of the leukotriene C(4) synthase associate with risk of ischemic cerebrovascular disease. METHODS AND RESULTS: We genotyped 10 592 individuals from the Danish general population, the Copenhagen City Heart Study. During 24 years of follow-up, 557 individuals developed ischemic cerebrovascular disease. The allele frequency was 0.07 for -1072 A and 0.29 for -444 C. Cumulative incidence for ischemic cerebrovascular disease was higher for -1072 AA versus GG genotype (log-rank: P=0.002), and lower for -444 CC versus AA genotype (log-rank: P=0.008). Combined genotypes showed corresponding cumulative incidence differences (log-rank: P=0.003). Multifactorially adjusted hazard ratios for ischemic cerebrovascular disease were 2.8(1.4 to 5.7) for -1072 AA versus GG genotype, 0.6(0.4 to 0.9) for -444 CC versus AA genotype, 2.5(1.2 to 5.4) for combined AA-AA versus GG-AA genotype, and 0.6(0.4 to 0.9) for combined GG-CC versus GG-AA genotype. Genotype did not associate with risk of deep venous thrombosis or severe carotid atherosclerosis, or with levels of platelets and coagulation factors. CONCLUSIONS: Leukotriene C(4) synthase -1072 AA genotype predict increased risk, whereas -444 CC genotype predict decreased risk of ischemic cerebrovascular disease
    Udgivelsesdato: 2008/5
    OriginalsprogEngelsk
    TidsskriftArteriosclerosis, Thrombosis, and Vascular Biology
    Vol/bind28
    Udgave nummer5
    Sider (fra-til)990-6
    Antal sider6
    ISSN1079-5642
    DOI
    StatusUdgivet - 2008

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