TY - JOUR

T1 - Low physical activity accentuates the effect of the FTO rs9939609 polymorphism on body fat accumulation

AU - Andreasen, Camilla H

AU - Stender-Petersen, Kirstine L

AU - Mogensen, Mette S

AU - Torekov, Signe S

AU - Wegner, Lise

AU - Andersen, Gitte

AU - Nielsen, Arne L

AU - Albrechtsen, Anders

AU - Borch-Johnsen, Knut

AU - Rasmussen, Signe S

AU - Clausen, Jesper O

AU - Sandbaek, Annelli

AU - Lauritzen, Torsten

AU - Hansen, Lars

AU - Jørgensen, Torben

AU - Pedersen, Oluf

AU - Hansen, Torben

N1 - Keywords: Adipose Tissue; Adult; Body Mass Index; Denmark; Diabetes Mellitus, Type 2; Female; Genetic Variation; Genotype; Glucose Intolerance; Humans; Linkage Disequilibrium; Male; Middle Aged; Motor Activity; Obesity; Odds Ratio; Oxo-Acid-Lyases; Polymorphism, Genetic; Reference Values

PY - 2008

Y1 - 2008

N2 - OBJECTIVE: Three independent studies have shown that variation in the fat mass and obesity-associated (FTO) gene associates with BMI and obesity. In the present study, the effect of FTO variation on metabolic traits including obesity, type 2 diabetes, and related quantitative phenotypes was examined. RESEARCH DESIGN AND METHODS: The FTO rs9939609 polymorphism was genotyped in a total of 17,508 Danes from five different study groups. RESULTS: In studies of 3,856 type 2 diabetic case subjects and 4,861 normal glucose-tolerant control subjects, the minor A-allele of rs9939609 associated with type 2 diabetes (odds ratio 1.13 [95% CI 1.06-1.20], P = 9 x 10(-5)). This association was abolished when adjusting for BMI (1.06 [0.97-1.16], P = 0.2). Among 17,162 middle-aged Danes, the A-allele associated with overweight (1.19 [1.13-1.24], P = 1 x 10(-12)) and obesity (1.27 [1.20-1.34], P = 2 x 10(-16)). Furthermore, obesity-related quantitative traits such as body weight, waist circumference, fat mass, and fasting serum leptin levels were significantly elevated in A-allele carriers. An interaction between the FTO rs9939609 genotype and physical activity (P = 0.007) was found, where physically inactive homozygous risk A-allele carriers had a 1.95 +/- 0.3 kg/m(2) increase in BMI compared with homozygous T-allele carriers. CONCLUSIONS: We validate that variation in FTO is associated with type 2 diabetes when not adjusted for BMI and with an overall increase in body fat mass. Furthermore, low physical activity seems to accentuate the effect of FTO rs9939609 on body fat accumulation.

AB - OBJECTIVE: Three independent studies have shown that variation in the fat mass and obesity-associated (FTO) gene associates with BMI and obesity. In the present study, the effect of FTO variation on metabolic traits including obesity, type 2 diabetes, and related quantitative phenotypes was examined. RESEARCH DESIGN AND METHODS: The FTO rs9939609 polymorphism was genotyped in a total of 17,508 Danes from five different study groups. RESULTS: In studies of 3,856 type 2 diabetic case subjects and 4,861 normal glucose-tolerant control subjects, the minor A-allele of rs9939609 associated with type 2 diabetes (odds ratio 1.13 [95% CI 1.06-1.20], P = 9 x 10(-5)). This association was abolished when adjusting for BMI (1.06 [0.97-1.16], P = 0.2). Among 17,162 middle-aged Danes, the A-allele associated with overweight (1.19 [1.13-1.24], P = 1 x 10(-12)) and obesity (1.27 [1.20-1.34], P = 2 x 10(-16)). Furthermore, obesity-related quantitative traits such as body weight, waist circumference, fat mass, and fasting serum leptin levels were significantly elevated in A-allele carriers. An interaction between the FTO rs9939609 genotype and physical activity (P = 0.007) was found, where physically inactive homozygous risk A-allele carriers had a 1.95 +/- 0.3 kg/m(2) increase in BMI compared with homozygous T-allele carriers. CONCLUSIONS: We validate that variation in FTO is associated with type 2 diabetes when not adjusted for BMI and with an overall increase in body fat mass. Furthermore, low physical activity seems to accentuate the effect of FTO rs9939609 on body fat accumulation.

U2 - 10.2337/db07-0910

DO - 10.2337/db07-0910

M3 - Journal article

C2 - 17942823

VL - 57

SP - 95

EP - 101

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 1

ER -