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Human Molecular Genetics Advance Access originally published online on September 23, 2003
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Human Molecular Genetics, 2003, Vol. 12, No. 22 2923-2929
DOI: 10.1093/hmg/ddg318
© 2003 Oxford University Press

Interaction between a peroxisome proliferator-activated receptor {gamma} gene polymorphism and dietary fat intake in relation to body mass

Asli Memisoglu1,*, Frank B. Hu2, Susan E. Hankinson1,3, JoAnn E. Manson1,3,4, Immaculata De Vivo1,3,5, Walter C. Willett1,2,3 and David J. Hunter1,2,3,4

1Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA, 2Department of Nutrition, Harvard School of Public Health, Boston, MA, USA, 3Channing Laboratory, Department of Medicine, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA, 4Division of Preventive Medicine, Department of Medicine, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA and 5Harvard Center for Cancer Prevention, Boston, MA, USA

Received June 23, 2003; Revised August 22, 2003; Accepted September 10, 2003

The peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) is a critical regulator of adipogenesis. PPAR{gamma}+/- mice are resistant to high-fat diet-induced obesity and thus PPAR{gamma} may mediate physiological responses to dietary fat in other mammals. The aim of this study was to determine whether the human PPAR{gamma} proline to alanine substitution polymorphism (Pro12Ala) modifies the association between dietary fat and adiposity and plasma lipids. Subjects (n=2141) were controls selected for three case–control studies nested within the Nurses' Health Study, a large ongoing prospective cohort study. Associations between intake of total fat, fat subtypes and BMI were different in PPAR{gamma} 12Ala variant allele-carriers compared with non-carriers. Among homozygous wild-type Pro/Pro individuals, those in the highest quintile of total fat intake, had significantly higher mean body mass index (BMI) compared with those in the lowest quintile (27.3 versus 25.4 kg/m2, respectively; P-trend<0.0001) whereas among 12Ala variant allele-carriers there was no significant trend observed between dietary fat intake and BMI (P-trend=0.99; P-interaction=0.003). In contrast, intake of monounsaturated fat was not associated with BMI among homozygous wild-type women but was inversely associated with BMI among 12Ala variant allele-carriers (mean in lowest quintile=27.6 versus mean in highest quintile=25.5 kg/m2; P-trend=0.006; P-interaction=0.003). The relationship between dietary fat intake and plasma lipid concentrations also differed according to PPAR{gamma} genotype. These data suggest that PPAR{gamma} genotype is an important factor in physiological responses to dietary fat in humans.

* To whom correspondence should be addressed at: Harvard School of Public Health, 677 Huntington Avenue, Bldg II Rm 105, Boston, MA 02115, USA. Fax: +1 6174321722; Email: amemisog{at}hsph.harvard.edu


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