Ala12 variant of the peroxisome proliferator-activated receptor- 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 infarction

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 receptorgene (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. Am J Clin Nutr 2007;86:1238–42.