title: Interaction between obesity and the NFKB1 - 94ins/delATTG promoter polymorphism in relation to incident acute coronary syndrome: a follow up study in three independent cohorts.
abstract: BACKGROUND
  The NF-κB transcription factor family regulates several genes encoding pro-inflammatory and anti-inflammatory proteins in adipose tissues and in atherosclerotic plaques. The deletion variant allele of the NFKB1 - 94ins/delATTG promoter polymorphism leads to lower transcript levels of the p50 subunit, and the variant allele has been associated with the risk of several inflammatory diseases as well as coronary heart disease where inflammation is important in the pathogenesis. The objective of this study was to explore the potential interaction between the NFKB1-94ins/delATTG promoter polymorphism and general, abdominal, and gluteofemoral obesity in relation to the risk of incident acute coronary syndrome (ACS) in three large independent cohorts.
  
  
  RESULTS
  The analyses were conducted in the Danish prospective study Diet, Cancer and Health and the two US based cohorts; Nurses' Health Study and Health Professionals Follow-up Study. We conducted sex stratified analyses that included 1202 male and 708 female cases of incident ACS. We observed a positive association for general and abdominal obesity with risk of incident ACS, independent of genotype in both genders. Gluteofemoral obesity was negatively associated with ACS risk in women independent of genotype, whereas there was no clear association for men. We calculated the relative excess risk due to interaction (RERI) and observed a statistically significant excess risk among men jointly exposed to general or abdominal obesity and the variant allele of the NFKB1-94ATTG polymorphism, whereas there was a tendency towards sub-additivity for gluteofemoral obesity. The excess risks in all analyses were, however, small and could not clearly be demonstrated in women.
  
  
  CONCLUSIONS
  The variant allele of the NFKB1-94ins/delATTG promoter polymorphism did not substantially modify the association between obesity and incident ACS.
authors.affiliation: Department of Cardiology, Center for Cardiovascular Research, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark. Jakob.stegger@rn.dk
authors.forename: Jakob Gerhard
authors.initials: JG
authors.lastname: Stegger
authors.forename: Erik Berg
authors.initials: EB
authors.lastname: Schmidt
authors.forename: Tina Landsvig
authors.initials: TL
authors.lastname: Berentzen
authors.forename: Anne
authors.initials: A
authors.lastname: Tjønneland
authors.forename: Ulla
authors.initials: U
authors.lastname: Vogel
authors.forename: Eric
authors.initials: E
authors.lastname: Rimm
authors.forename: Thorkild I A
authors.initials: TI
authors.lastname: Sørensen
authors.forename: Kim
authors.initials: K
authors.lastname: Overvad
authors.forename: Majken K
authors.initials: MK
authors.lastname: Jensen
mesh_terms: D054058:Acute Coronary Syndrome / Q000150:complications / Q000235:genetics*; D000328:Adult; D000368:Aged; D001483:Base Sequence; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016254:Mutagenesis, Insertional; D016328:NF-kappa B / Q000235:genetics*; D052002:NF-kappa B p50 Subunit / Q000235:genetics; D009765:Obesity / Q000150:complications / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011446:Prospective Studies; D012044:Regression Analysis; D017384:Sequence Deletion
chemical_list: D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit