The NFKB1 ATTG ins/del polymorphism and risk of coronary heart disease in three independent populations

Ulla Vogel, Majken Jensen, Karen Margrete Due, Eric B. Rimm, Håkan Wallin, Michael René Skjelbo Nielsen, Anne Pernille Toft-Petersen, Anne Tjønneland, Kim Overvad

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review


    Aim: Inflammation is a risk factor for coronary heart disease (CHD). A common deletion-allele in the promoter region of NFKB1 results in lower protein levels of the NF-kappa B p50 subunit. Recent evidence suggests that the NF-kappa B p50 dimer has anti-inflammatory effects. We aimed to investigate the association of the functional ATTG NFKB1 insertion/deletion variant with risk of CHD in three independent prospective studies of generally healthy men and women.

    Methods and results: The NFKB1 ins/del polymorphism was genotyped in studies of CHD nested within the Diet, Cancer and Health (DCH) study, the Health Professionals Follow-up (HPFS) and the Nurses' Health (NHS) studies, totaling 1008, 428 and 439 cases, respectively. The minor allele frequency in the combined sample was 0.38 among controls. In a pooled analysis, the relative risk (RR) among heterozygous men and women was 1.22 (95% CI: 1.07-1.40), compared to the most common ins/ins genotype. The RR among homozygotes was 1.20 (95% CI: 0.94-1.53). There was no evidence of an allele-dosage effect, and in a dominant model the RR among del-allele carriers was 1.22 (95% CI: 1.07-1.39). The risk was similar in women and men (RR was 1.20 in women and 1.23 in men, respectively). The NFKB1 variant was not associated with plasma lipid levels, but del-carriers had lower levels of C-reactive protein.

    Conclusions: The NFKB1 promoter variant, previously shown to cause partial depletion of NF-kappa B p50, was associated with a higher risk of CHD in three independent prospective studies of generally healthy Caucasians
    Udgave nummer1
    Sider (fra-til)200-204
    StatusUdgivet - 2011

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