Association of the Pro12Ala Polymorphism in the PPAR-γ2 Gene With 3-Year Incidence of Type 2 Diabetes and Body Weight Change in the Finnish Diabetes Prevention Study

• Published in: Diabetes (New York, N.Y.) Vol. 51; no. 8; pp. 2581 - 2586
• Main Authors: Lindi, Virpi I, Uusitupa, Matti I.J, Lindstrom, Jaana, Louheranta, Anne, Eriksson, Johan G, Valle, Timo T, Hamalainen, Helena, Ilanne-Parikka, Pirjo, Keinanen-Kiukaanniemi, Sirkka, Laakso, Markku, Tuomilehto, Jaakko
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.08.2002
• Subjects: Biological and medical sciences; Complications and side effects; Development and progression; Diabetes; Diabetes mellitus; Diabetes. Impaired glucose tolerance; Dietary fiber; Dietary fibre; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Fiber in human nutrition; Glucose intolerance; Health aspects; Low fat diet; Medical sciences; Type 2 diabetes; Finland; Endocrinopathy; Association; Gene; Body weight; Finnish; Non insulin dependent diabetes; PPAR-γ2 receptor; Polymorphism
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/diabetes.51.8.2581

Association of the Pro12Ala Polymorphism in the PPAR-γ2 Gene With 3-Year Incidence of Type 2 Diabetes and Body Weight Change in the Finnish Diabetes Prevention Study Virpi I. Lindi 1 , Matti I.J. Uusitupa 1 , Jaana Lindström 2 , Anne Louheranta 1 , Johan G. Eriksson 2 , Timo T. Valle 2 , Helena Hämäläinen 3 , Pirjo Ilanne-Parikka 4 , Sirkka Keinänen-Kiukaanniemi 5 , Markku Laakso 6 , Jaakko Tuomilehto 7 and for the Finnish Diabetes Prevention Study Group 1 Department of Clinical Nutrition, University of Kuopio and Kuopio University Hospital, Kuopio, Finland 2 Department of Epidemiology and Health Promotion, Diabetes and Genetic Epidemiology Unit, National Public Health Institute, Helsinki, Finland 3 Social Insurance Institution, Research and Development Centre, Turku, Finland 4 Department of Medicine, University of Tampere and Finnish Diabetes Association, Tampere, Finland 5 Department of Public Health Science and General Practice, University of Oulu, Oulu University Hospital, and the Department of Sports Medicine, Oulu Deaconess Institute, Oulu, Finland 6 Department of Medicine, University of Kuopio, Kuopio, Finland 7 Department of Public Health, University of Helsinki, Helsinki, Finland Abstract The association of the Pro12Ala polymorphism of the PPAR-γ2 gene with the incidence of type 2 diabetes was investigated in 522 subjects with impaired glucose tolerance (IGT) participating in the Finnish Diabetes Prevention Study. Subjects were randomized to either an intensive diet and exercise group or a control group. By 3 years of intervention, the odds ratio of the development of type 2 diabetes for subjects with the Ala12 allele was 2.11-fold compared with that for subjects with the Pro12Pro genotype (95% CI 1.20–3.72). The risk for type 2 diabetes increased also in subjects who gained weight or belonged to the control group. In the intervention group, subjects with the Ala12Ala genotype lost more weight during the follow-up than subjects with other genotypes (Pro12Pro vs. Ala12Ala P = 0.043), and none of subjects with the Ala12Ala genotype developed type 2 diabetes in this group. In conclusion, the Ala12 allele may predispose to the development of type 2 diabetes in obese subjects with IGT. However, beneficial changes in diet, increases in physical activity, and weight loss may reverse, to some extent, the diabetogenic impact of the Ala12 allele, possibly due to an improved insulin sensitivity. Footnotes Address correspondence and reprint requests to Virpi Lindi, M.Sc., University of Kuopio, Department of Clinical Nutrition, P.O. Box 1627, FIN-70211 Kuopio, Finland. E-mail: virpi.lindi{at}uku.fi . Received for publication 2 November 2001 and accepted in revised form 26 April 2002. DPS, Finnish Diabetes Prevention Study; HBMI, a higher BMI group; GLM, general linear model; HOMA-IR, homeostasis model assessment for insulin resistance; IGT, impaired glucose tolerance; LBMI, a lower BMI group; OGTT, oral glucose tolerance test; PPAR-γ, peroxisome proliferator-activated receptor-γ; SSCP, single-strand conformation polymorphism. DIABETES