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.
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).


METHODS
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.
Ruiz-Narváez
Edward A
EA
Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA.
Kraft
Peter
P
Campos
Hannia
H
D000273:Adipose Tissue / Q000737:chemistry* / Q000378:metabolism; D016022:Case-Control Studies; D002849:Chromatography, Gas; D016001:Confidence Intervals; D003364:Costa Rica / Q000453:epidemiology; D053938:DNA Fragmentation; D005231:Fatty Acids, Unsaturated / Q000032:analysis* / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008066:Lipolysis; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics* / Q000378:metabolism; D016017:Odds Ratio; D047495:PPAR gamma / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D011795:Surveys and Questionnaires; D014280:Triglycerides / Q000378:metabolism
D005231:Fatty Acids, Unsaturated; D047495:PPAR gamma; D014280:Triglycerides