title: Association of TNF-alpha serum levels and TNFA promoter polymorphisms with risk of myocardial infarction.
abstract: Elevated levels of tumor necrosis factor-alpha (TNF-alpha), and presence of polymorphisms of the TNFA gene have been implicated in cardiovascular disease pathogenesis. We explored the relationship between polymorphisms in the TNFA gene (-1031C/T, -863C/A -857T/C, -308G/A, -238G/A), protein levels of TNF-alpha and their association to myocardial infarction (MI) using a sample of 1213 post-MI patients and 1561 healthy controls. MI risk was higher among men with elevated TNF-alpha levels, with the highest compared to the lowest TNF-alpha quartile giving a 70% risk increase (OR [95% CI]: 1.7 [1.1; 2.6]). Obese subjects who also had elevated TNF-alpha levels were at even higher risk for MI (OR [95% CI]: 3.4 [2.1; 5.6]). Higher TNF-alpha levels were seen among smokers (but not among non-smokers) carrying the -857T allele. Furthermore, a rare haplotype occurred more frequently among the cases than the controls. Elevated TNF-alpha levels are associated with increased MI risk. Obese subjects with elevated TNF-a levels, and carriers of polymorphisms in or near TNFA are particularly susceptible to the hazards of smoking, results which may have implications for cardiovascular preventive measures.
authors.affiliation: Unit of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institute, Box 210, S-171 77 Stockholm, Sweden. Anna.Bennet@ki.se
authors.forename: A M
authors.initials: AM
authors.lastname: Bennet
authors.forename: M C
authors.initials: MC
authors.lastname: van Maarle
authors.forename: J
authors.initials: J
authors.lastname: Hallqvist
authors.forename: R
authors.initials: R
authors.lastname: Morgenstern
authors.forename: J
authors.initials: J
authors.lastname: Frostegård
authors.forename: B
authors.initials: B
authors.lastname: Wiman
authors.forename: J A
authors.initials: JA
authors.lastname: Prince
authors.forename: U
authors.initials: U
authors.lastname: de Faire
mesh_terms: D000368:Aged; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000453:epidemiology* / Q000235:genetics*; D009765:Obesity / Q000097:blood / Q000453:epidemiology / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D012307:Risk Factors; D017678:Sex Distribution; D012907:Smoking / Q000453:epidemiology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood* / Q000235:genetics*
chemical_list: D014409:Tumor Necrosis Factor-alpha