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Association of the peroxisome proliferator-activated receptor gamma gene with type 2 diabetes mellitus varies by physical activity among non-Hispanic whites from Colorado.

Nelson TL, Fingerlin TE, Moss LK, Barmada MM, Ferrell RE, Norris JM

Department of Health and Exercise Science, Colorado State University, Fort Collins, CO 80523, USA. tnelson@cahs.colostate.edu

The objective of the study was to test for an association between type 2 diabetes mellitus (T2DM) and the Pro12Ala polymorphism in the peroxisome proliferator-activated receptor gamma gene (PPAR-gamma) in families from Colorado. We were also interested in whether there was any modification by diet or physical activity. We studied 216 Hispanic pedigrees (1850 nuclear families) and 236 non-Hispanic white (NHW) pedigrees (1240 families) from the San Luis Valley and Denver, CO. We genotyped the Pro12Ala polymorphism of the PPAR-gamma gene. Historical physical activity (average metabolic equivalent task units per week) as well as average dietary intake over the past year was assessed by self-report. Using the family-based association test, we found that in NHWs the Pro12 allele was associated with T2DM only among those with low physical activity (P = .006), or with high polyunsaturated fat intake (P = .034). A significant interaction between low physical activity and the Pro12 allele in association with T2DM was also detected using generalized estimating equations models (P = .022). Furthermore, after stratifying by physical activity similar to the family-based association test, we found the Pro12 allele was significantly associated with T2DM in those with low physical activity (odds ratio, 2.37; 95% confidence interval, 1.14-4.94). There may be a gene-environment interaction between the Pro12 allele of the PPAR-gamma gene and physical activity that results in increased risk of T2DM in NHWs.

Published 12 February 2007 in Metabolism, 56(3): 388-93.
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