Ala12 variant of the peroxisome proliferator-activated receptor-{gamma} gene (PPARG) is associated with higher polyunsaturated fat in adipose tissue and attenuates the protective effect of polyunsaturated fat intake on the risk of myocardial infarcti

摘要

BACKGROUND: Intake of polyunsaturated fat is protective against the development of coronary heart disease. Less is known about the genetic variation modulating this association. The Ala12 allele of the peroxisome proliferator-activated receptor-gamma gene (PPARG) decreases the lipolysis of triacylglycerols in adipose tissue, which results in the accumulation of fatty acids in adipocytes. OBJECTIVE: We aimed to determine whether the Pro12Ala polymorphism interacts with polyunsaturated fat intake to affect the risk of myocardial infarction (MI). DESIGN: Cases (n = 1805) with a first nonfatal acute MI and population-based controls matched by age, sex, and area of residence (n = 1805) living in Costa Rica were genotyped for the PPARG Pro12Ala genetic polymorphism. Polyunsaturated fat intake was determined by use of a validated food-frequency questionnaire and by gas chromatography analysis of adipose tissue. Odds ratios and 95 CIs for MI were estimated by use of logistic regression. RESULTS: The relative allele frequencies of the Ala12 allele were 10 in controls and 11 in cases. Odds ratios (95 CI) for MI per each 5 increase in energy from polyunsaturated fat were 0.66 (0.53, 0.82) in Pro12/Pro12 subjects and 0.93 (0.61, 1.42) in carriers of the Ala12 allele (P for interaction = 0.03). Increments (95 CI) of polyunsaturated fat in adipose tissue per 5 increment in dietary intake were 5.4 (4.9, 5.9) in Pro12/Pro12 homozygotes, 6.9 (6.0, 7.9) in Pro12/Ala12 heterozygotes, and 7.7 (3.2, 12.2) in Ala12/Ala12 homozygotes (P for interaction = 0.016). CONCLUSIONS: The protective effect of polyunsaturated fat intake on MI is attenuated in carriers of the Ala12 allele of PPARG.