Association of the Pro12Ala polymorphism in the PPAR-gamma2 gene with 3-year incidence of type 2 diabetes and body weight change in the Finnish Diabetes Prevention Study.
The association of the Pro12Ala polymorphism of the PPAR-gamma2 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.
Lindi
Virpi I
VI
Department of Clinical Nutrition, University of Kuopio and Kuopio University Hospital, Kuopio, Finland. virpi.lindi@uku.fi
Uusitupa
Matti I J
MI
Lindström
Jaana
J
Louheranta
Anne
A
Eriksson
Johan G
JG
Valle
Timo T
TT
Hämäläinen
Helena
H
Ilanne-Parikka
Pirjo
P
Keinänen-Kiukaanniemi
Sirkka
S
Laakso
Markku
M
Tuomilehto
Jaakko
J
D000409:Alanine; D019943:Amino Acid Substitution; D001786:Blood Glucose / Q000378:metabolism; D001824:Body Constitution; D015992:Body Mass Index; D001835:Body Weight / Q000235:genetics*; D003920:Diabetes Mellitus / Q000517:prevention & control*; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D005387:Finland / Q000453:epidemiology; D005838:Genotype; D018149:Glucose Intolerance / Q000235:genetics; D006801:Humans; D015994:Incidence; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D011110:Polymorphism, Genetic; D011392:Proline; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D012044:Regression Analysis; D014157:Transcription Factors / Q000235:genetics*
D001786:Blood Glucose; D007328:Insulin; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D011392:Proline; D000409:Alanine