The NFKB1 ATTG ins/del Polymorphism and Risk of Coronary Heart Disease in Three Independent Populations
Due, Karen Margrete
Rimm, Eric Bruce::0ab2926c8242f35e5a982e3cf59f4987::600
Nielsen, Michael R. S.
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CitationVogel, Ulla, Majken K. Jensen, Karen Margrete Due, Eric B. Rimm, Håkan Wallin, Michael R.S. Nielsen, Anne-Pernille T. Pedersen, Anne Tjønneland, and Kim Overvad. 2011. “The NFKB1 ATTG Ins/Del Polymorphism and Risk of Coronary Heart Disease in Three Independent Populations.” Atherosclerosis 219 (1): 200–204. https://doi.org/10.1016/j.atherosclerosis.2011.06.018.
AbstractAim: 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. Published by Elsevier Ireland Ltd.
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