title: The NFKB1 ATTG ins/del polymorphism and risk of coronary heart disease in three independent populations.
abstract: OBJECTIVE
  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-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.
  
  
  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-κB p50, was associated with a higher risk of CHD in three independent prospective studies of generally healthy Caucasians.
authors: National Research Centre for the Working Environment, Copenhagen, Denmark. ubv@nrcwe.dk
authors: Ulla
authors: U
authors: Vogel
authors: Majken K
authors: MK
authors: Jensen
authors: Karen Margrete
authors: KM
authors: Due
authors: Eric B
authors: EB
authors: Rimm
authors: Håkan
authors: H
authors: Wallin
authors: Michael R S
authors: MR
authors: Nielsen
authors: Anne-Pernille T
authors: AP
authors: Pedersen
authors: Anne
authors: A
authors: Tjønneland
authors: Kim
authors: K
authors: Overvad
mesh_terms: D000328:Adult; D000368:Aged; D003327:Coronary Disease / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D003718:Denmark / Q000453:epidemiology; D005260:Female; D018628:Gene Dosage; D020022:Genetic Predisposition to Disease; D006801:Humans; D054643:INDEL Mutation; D008297:Male; D008875:Middle Aged; D052002:NF-kappa B p50 Subunit / Q000235:genetics*; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012306:Risk; D017384:Sequence Deletion; D014481:United States / Q000453:epidemiology
chemical_list: D052002:NF-kappa B p50 Subunit; C489548:NFKB1 protein, human