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Evidence of Interaction Between PPARG2 and HNF4A Contributing to Variation in Insulin Sensitivity in Mexican Americans

Year: 2007
Type: article
Study design: Observational Study
Abstract: OBJECTIVE: We hypothesized that interaction between PPARG2 Pro12Ala and variants in the promoter region of HNF4A are associated with type 2 diabetes-related quantitative traits in Mexican-American families of a proband with previous gestational diabetes. RESEARCH DESIGN AND METHODS: The BetaGene project genotyped PPARG2 Pro12Ala and nine HNF4A single nucleotide polymorphisms (SNPs) in 473 individuals in 89 families. Members of the proband generation had fasting glucose <126 mg/dl and were phenotyped by oral and intravenous glucose tolerance tests. RESULTS: Neither PPARG2 Pro12Ala nor any of the nine HNF4A SNPs were independently associated with type 2 diabetes-related quantitative traits. However, the interaction between PPARG2 Pro12Ala and HNF4A rs2144908 was significantly associated with both insulin sensitivity (S(I)) (Bonferroni P = 0.0006) and 2-h insulin (Bonferroni P = 0.039). Subjects with at least one PPARG2 Ala allele and homozygous for the HNF4A rs2144908 A allele had 40% higher S(I) compared with individuals with at least one G allele. S(I) did not vary by rs2144908 genotype among PPARG2 Pro/Pro. The interaction result for S(I) was replicated by the Insulin Resistance Atherosclerosis Family Study (P = 0.018) in their San Antonio sample (n = 484) where subjects with at least one PPARG2 Ala allele and homozygous for the HNF4A rs2144908 A allele had a 29% higher S(I) compared with individuals with at least one G allele. However, the interaction was not replicated in their San Luis Valley sample (n = 496; P = 0.401). CONCLUSIONS: Together, these results suggest that variation in PPARG2 and HNF4A may interact to regulate insulin sensitivity in Mexican Americans at risk for type 2 diabetes.
Source: Diabetes
DOI: 10.2337/db07-0848
Authors: Mary Helen Black, Tasha E. Fingerlin, Hooman Allayee, Weiming Zhang, Anny H. Xiang, Enrique Trigo, Jaana Hartiala, Allison B. Lehtinen, Steven M. Haffner, Richard N. Bergman, Richard C. McEachin, Siri L. Kjos, Jean M. Lawrence, Thomas A. Buchanan, Richard M. Watanabe
Institutions: University of Southern California, University of Colorado Denver, Wake Forest University Health Sciences, Wake Forest University, The University of Texas at San Antonio Health Science Center, University of Michigan, Michigan Medicine, University of California, Los Angeles, Harbor–UCLA Medical Center, Kaiser Permanente
Language: English
Open Access status: green
Funders: National Institutes of Health, National Heart, Lung, and Blood Institute, National Institute on Drug Abuse, National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Research Resources
Awards: Genetics of Adiposity and Glucose Homeostastis, G1377307154, G1574475437, G2145651488, G2665690755, RESEARCH FACILITIES IMPROVEMENT PROGRAM AND REMODELING, Genetics of Beta Cell Failure in Mexican Americans, National Center for Integrative Biomedical Informatics(RMI), G4908468896, G4929280640, Molecular genetics of glucose homeostasis and fat, Genetics of Adiposity and Glucose Homeostasis, General Clinical Research Center, IRAS FAMILY STUDY--GENETICS OF INSULIN RESISTANCE, Genetics of Adiposity and Glucose Homeostasis, G668418727, G6703968059, Quantitation of Factors Regulating Glucose Tolerance, G7816041120, EXTRAMURAL RESEARCH FACILITIES CONTRUCTION PROJECT, EXTRAMURAL RESEARCH FACILITIES CONSTRUCTION
OpenAlex ID: W2150021896
FWCI: 1.853
Cites: 45
Cited by: 51
Related to: 10