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 infarction

Am J Clin Nutr. 2007 Oct;86(4):1238-42. doi: 10.1093/ajcn/86.4.1238.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adipose Tissue / chemistry*
  • Adipose Tissue / metabolism
  • Case-Control Studies
  • Chromatography, Gas
  • Confidence Intervals
  • Costa Rica / epidemiology
  • DNA Fragmentation
  • Fatty Acids, Unsaturated / analysis*
  • Fatty Acids, Unsaturated / metabolism
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genetic Variation*
  • Genotype
  • Humans
  • Lipolysis
  • Logistic Models
  • Male
  • Middle Aged
  • Myocardial Infarction / genetics*
  • Myocardial Infarction / metabolism
  • Odds Ratio
  • PPAR gamma / genetics*
  • PPAR gamma / metabolism
  • Polymorphism, Single Nucleotide*
  • Risk Factors
  • Surveys and Questionnaires
  • Triglycerides / metabolism

Substances

  • Fatty Acids, Unsaturated
  • PPAR gamma
  • Triglycerides