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

Publication: Research - peer-reviewJournal article – Annual report year: 2011

  • Author: Vogel, Ulla Birgitte

    National Food Institute, Technical University of Denmark

  • Author: Jensen, Majken K.

    Harvard School of Public Health, Department of Nutrition

  • Author: Due, Karen Margrete

    Aarhus University

  • Author: Rimm, Eric B.

    Harvard School of Public Health

  • Author: Wallin, Håkan

    National Research Centre for the Working Environment, Denmark

  • Author: Nielsen, Michael R.S.

    Aarhus University

  • Author: Pedersen, Anne-Pernille T.

    Aarhus University

  • Author: Tjønneland, Anne

    Danish Cancer Society, Denmark

  • Author: Overvad, Kim

    Aarhus University

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AimInflammation 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-κB p50 subunit. Recent evidence suggests that the NF-κB 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 resultsThe 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. ConclusionsThe NFKB1 promoter variant, previously shown to cause partial depletion of NF-κB p50, was associated with a higher risk of CHD in three independent prospective studies of generally healthy Caucasians.
Original languageEnglish
JournalAtherosclerosis
Publication date2011
Volume219
Issue1
Pages200-204
ISSN0021-9150
DOIs
StatePublished
CitationsWeb of Science® Times Cited: 10

Keywords

  • Polymorphism, NF-kB, Population-based, Inflammation
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