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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.
- Source :
-
PloS one [PLoS One] 2013 May 09; Vol. 8 (5), pp. e63004. Date of Electronic Publication: 2013 May 09 (Print Publication: 2013). - Publication Year :
- 2013
-
Abstract
- Introduction: 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.<br />Methods and 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.<br />Conclusion: The variant allele of the NFKB1-94ins/delATTG promoter polymorphism did not substantially modify the association between obesity and incident ACS.
- Subjects :
- Acute Coronary Syndrome complications
Adult
Aged
Base Sequence
Female
Follow-Up Studies
Humans
Male
Middle Aged
Mutagenesis, Insertional
NF-kappa B p50 Subunit genetics
Obesity complications
Prospective Studies
Regression Analysis
Sequence Deletion
Acute Coronary Syndrome genetics
Genetic Predisposition to Disease genetics
NF-kappa B genetics
Obesity genetics
Polymorphism, Genetic
Promoter Regions, Genetic genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 8
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 23671649
- Full Text :
- https://doi.org/10.1371/journal.pone.0063004