Journal article
The NFKB1 ATTG ins/del polymorphism and risk of coronary heart disease in three independent populations
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.
Language: | English |
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Publisher: | Elsevier BV |
Year: | 2011 |
Pages: | 200-204 |
ISSN: | 18791484 , 00219150 , 01700626 , 18785050 and 15675688 |
Types: | Journal article |
DOI: | 10.1016/j.atherosclerosis.2011.06.018 |
ORCIDs: | 0000-0001-6429-7921 |
Adult Aged Coronary Disease Denmark Female Gene Dosage Genetic Predisposition to Disease Humans INDEL Mutation Male Middle Aged NF-kappa B p50 Subunit NFKB1 protein, human NFkappaB Polymorphism, Genetic Prospective Studies Risk Sequence Deletion United States inflammation polymorphism population-based