title: Peroxisome proliferator-activated receptor-gamma2 P12A polymorphism and risk of coronary heart disease in US men and women.
abstract: OBJECTIVE
  Activation of the peroxisome proliferator-activated receptor-gamma (PPARgamma) improves insulin sensitivity and exerts antiatherogenic effects. A common alanine for proline substitution at codon 12 in the PPARG2 gene is related to lower receptor activity. Studies suggest that the A12 allele is associated with reduced risk of type 2 diabetes; however, data on the risk of coronary heart disease (CHD) are scarce and controversial.
  
  
  RESULTS
  We examined the relationship between PPARG2 P12A and CHD risk in women (Nurses' Health Study) and men (Health Professionals Follow-Up Study) in nested case control settings. Among participants free of cardiovascular disease at baseline, 249 women and 266 men developed nonfatal myocardial infarction (MI) or fatal CHD during 8 and 6 years of follow-up, respectively. Using risk-set sampling, controls were selected 2:1 matched on age, smoking, and date of blood draw. The relative risk (RR) of nonfatal MI or fatal CHD of carriers compared with noncarriers of the A12 allele was 1.17 (95% CI, 0.82 to 1.68) among women and 1.44 (95% CI, 1.00 to 2.07) among men (pooled RR, 1.30 [95% CI, 1.00 to 1.67]). We found a significantly increased risk associated with the A12 allele among individuals with a body mass index > or =25 kg/m2 (women: RR, 1.88; 95% CI, 1.01 to 3.50; men: RR, 1.55; 95% CI, 0.92 to 2.60; pooled: RR, 1.68; 95% CI, 1.13 to 2.50) but not among those <25 kg/m2 (pooled RR, 0.86; 95% CI, 0.37 to 1.97; P heterogeneity overweight versus nonoverweight 0.16).
  
  
  CONCLUSIONS
  These data do not support the hypothesis that the A12 allele is associated with a decreased risk of CHD. The potential interaction between PPARG2 P12A, overweight, and increased CHD risk needs further evaluation.
authors.affiliation: Department of Nutrition and Epidemiology, Harvard School of Public Health, Boston, Mass, USA. pischon@mail.dife.de
authors.forename: Tobias
authors.initials: T
authors.lastname: Pischon
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Pai
authors.forename: JoAnn E
authors.initials: JE
authors.lastname: Manson
authors.forename: Frank B
authors.initials: FB
authors.lastname: Hu
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Rexrode
authors.forename: David
authors.initials: D
authors.lastname: Hunter
authors.forename: Eric B
authors.initials: EB
authors.lastname: Rimm
mesh_terms: D000328:Adult; D000368:Aged; D003327:Coronary Disease / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology / Q000235:genetics; D009765:Obesity / Q000453:epidemiology / Q000235:genetics; D047495:PPAR gamma / Q000235:genetics*; D011110:Polymorphism, Genetic; D015995:Prevalence; D011446:Prospective Studies; D012307:Risk Factors; D017678:Sex Distribution; D014481:United States / Q000453:epidemiology; D015430:Weight Gain / Q000235:genetics
chemical_list: D047495:PPAR gamma