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

Ulla Birgitte Vogel, Majken K. Jensen, Karen Margrete Due, Eric B. Rimm, Håkan Wallin, Michael R.S. Nielsen, Anne-Pernille T. Pedersen, Anne Tjønneland, Kim Overvad

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

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
Volume219
Issue number1
Pages (from-to)200-204
ISSN0021-9150
DOIs
Publication statusPublished - 2011

Keywords

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

Fingerprint

Dive into the research topics of 'The NFKB1 ATTG ins/del polymorphism and risk of coronary heart disease in three independent populations'. Together they form a unique fingerprint.

Cite this