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SNPs in PPARG Associate with Type 2 Diabetes and Interact with Physical Activity

KILPELÄINEN, TUOMAS O.1; LAKKA, TIMO A.1,2; LAAKSONEN, DAVID E.1,3; LINDSTRÖM, JAANA4; ERIKSSON, JOHAN G.4,5; VALLE, TIMO T.4; HÄMÄLÄINEN, HELENA6; ILANNE-PARIKKA, PIRJO7,8; KEINÄNEN-KIUKAANNIEMI, SIRKKA9,10; LINDI, VIRPI11; TUOMILEHTO, JAAKKO4,5,12; UUSITUPA, MATTI11; LAAKSO, MARKKU3

Medicine & Science in Sports & Exercise: January 2008 - Volume 40 - Issue 1 - pp 25-33
doi: 10.1249/mss.0b013e318159d1cd
CLINICAL SCIENCES: Clinically Relevant

Purpose: To study the associations of seven single-nucleotide polymorphisms (SNPs) in the peroxisome proliferator-activated receptor gamma (PPARG) gene with the conversion from impaired glucose tolerance (IGT) to type 2 diabetes (T2D), and the interactions of the SNPs with physical activity (PA).

Methods: Overweight individuals with IGT who participated in the Finnish Diabetes Prevention Study (DPS) (N = 479) were followed, on average, 4.2 yr. PA was assessed yearly with a 12-month validated questionnaire.

Results: In Cox regression analyses, the rare alleles of rs17036314 and rs1801282 (Pro12Ala) predicted conversion to T2D (P = 0.038 and 0.037, respectively), but only rs17036314 predicted T2D after adjustment for baseline fasting glucose (P = 0.030). The change in the total amount of PA, stratified by median, modified the association of rs17036314 and rs1801282 with the risk of T2D during the intervention (P = 0.002 and 0.031, respectively, for interaction between PA change and genotype); an increase in PA seemed to remove the effect of the risk alleles. The distinct rs1152003 polymorphism interacted with the study group on the conversion to T2D (P = 0.027) and tended to increase the risk of T2D in the intervention group (P = 0.050). No interaction between rs1152003 and the change in PA was found.

Conclusions: The rs17036314, rs1801282 (Pro12Ala), and rs1152003 were associated with the risk of T2D in the DPS. Increased PA seemed to decrease the effect of the risk alleles of rs17036314 and rs1801282 on the conversion to T2D. The effect of rs1152003 was modified by other lifestyle changes or the lifestyle intervention as a whole.

1Institute of Biomedicine, Physiology, University of Kuopio, Kuopio, FINLAND; 2Kuopio Research Institute of Exercise Medicine, Kuopio, FINLAND; 3Department of Medicine, University of Kuopio and Kuopio University Hospital, Kuopio, FINLAND; 4Department of Health Promotion and Chronic Disease Prevention, Diabetes Unit, National Public Health Institute, Helsinki, FINLAND; 5Department of Public Health, University of Helsinki, Helsinki, FINLAND; 6Research Department, Social Insurance Institution, Turku, FINLAND; 7Finnish Diabetes Association, Tampere, FINLAND; 8Tampere University Hospital Research Unit, Tampere, FINLAND; 9Department of Public Health Science and General Practice, Unit of General Practice, Oulu University Hospital, Oulu, FINLAND; 10Department of Sports Medicine, Oulu Deaconess Institute, Oulu, FINLAND; 11School of Public Health and Clinical Nutrition, Clinical Nutrition, University of Kuopio, Kuopio, FINLAND; and 12South Ostrobothnia Central Hospital, Seinäjoki, FINLAND

Address for correspondence: Tuomas O. Kilpeläinen, MSc, Institute of Biomedicine, Physiology, University of Kuopio, Yliopistonranta 1 E, 70210 Kuopio, Finland; E-mail: tuomas.kilpelainen@uku.fi.

Submitted for publication March 2007.

Accepted for publication August 2007.

© 2008 American College of Sports Medicine