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Exp Clin Endocrinol Diabetes 2009; 117(9): 455-459
DOI: 10.1055/s-0029-1216352
Article

© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

Evidence for Interaction between PPARG Pro12Ala and PPARGC1A Gly482Ser Polymorphisms in Determining Type 2 Diabetes Intermediate Phenotypes in Overweight Subjects

S.-M. Ruchat 1 , 2 , S. J. Weisnagel 1 , 2 , M-C. Vohl 2 , T. Rankinen 3 , C. Bouchard 3 , L. Pérusse 1 , 2
  • 1Department of Preventive Medicine, Laval University, Quebec, Canada
  • 2Lipid Research Center, CHUL Research Center, Quebec, Canada
  • 3Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA
Further Information

Publication History

received 19.01.2009 first decision 18.02.2009

accepted 11.03.2009

Publication Date:
17 June 2009 (online)

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Abstract

Background: The peroxisome proliferator-activated receptor-γ (PPARG) Pro12Ala and the PPARG co-activator-1α (PPARGC1A) Gly482Ser polymorphisms (SNPs) have been associated with type 2 diabetes mellitus (T2DM) risk. We hypothesized that independent and interactive effects of the PPARG Pro12Ala and PPARGC1A Gly482Ser polymorphisms influence T2DM intermediate phenotypes.

Material and Methods: PPARG Pro12Ala and PPARGC1A Gly482Ser SNPs were studied in 680 non diabetic subjects who underwent a 75 g oral glucose tolerant test (OGTT). Glucose and insulin plasma levels in the fasting state and derived from the OGTT were included in the present study.

Results: We found significant independent effects of the PPARG and PPARGC1A variants on fasting insulin levels (p=0.02 for both), HOMA-IR (p=0.03 and p=0.02, respectively), insulin area under the curve (AUC) (p=0.007 and p=0.006, respectively) and 2-h glucose levels (p=0.02 for PPARGC1A). Furthermore, significant gene-gene interactions were found for fasting insulin, HOMA-IR and insulin AUC (p=0.03 for all). Carriers of the PPARGC1A Gly allele who were also PPARG Ala-carriers had higher fasting insulin levels (p=0.02), HOMA-IR (p=0.01) and insulin AUC (p=0.01) compared to the Ser/Ser-Ala+genotype combination, whereas no differences between the PPARGC1A genotypes among the PPARG Pro/Pro carriers were observed.

Conclusion: Together, these results showed that PPARG Pro12Ala and PPARGC1A Gly482Ser variants are associated, alone and in interaction, with insulin and glucose homeostasis and suggest that gene-gene interactions should be taken into account in candidate gene studies of T2DM to identify subjects with markedly different risks of developing the disease.

Key words

PPARG Pro12Ala - PPARGC1A Gly482Ser - interactions - T2DM-related phenotypes

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Correspondence

L. PérussePhD 

Department of Médecine sociale et préventive

Division de Kinésiologie

PEPS – 2300 rue de la Terrasse

Université Laval

Québec, QC, G1 V 0A6

Canada

Email: Louis.Perusse@kin.msp.ulaval.ca