TY - JOUR
T1 - Association of the beta3-adrenergic receptor Trp64Arg polymorphism with common metabolic traits: studies of 7605 middle-aged white people
AU - Gjesing, A. P.
AU - Andersen, G
AU - Borch-Johnsen, K
AU - Jørgensen, T
AU - Hansen, T
AU - Pedersen, Oluf
N1 - Keywords: Arginine; Denmark; Diabetes Mellitus, Type 2; European Continental Ancestry Group; Female; Genetic Variation; Genotype; Humans; Male; Middle Aged; Obesity; Polymorphism, Single Nucleotide; Receptors, Adrenergic, beta-3; Tryptophan
PY - 2008
Y1 - 2008
N2 - AIM/HYPOTHESIS: The functional variant Trp64Arg in the beta(3)-adrenergic receptor has previously been examined for association with obesity and insulin resistance with ambiguous results. For further evaluation the present study examined the impact of the Trp64Arg variant on the pathogenesis of type 2 diabetes and obesity in a relatively large, homogenous study population. METHODS: The Trp64Arg polymorphism was genotyped in 7605 Danish subjects using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Association was examined in case-control studies of obesity (1529 cases and 6049 controls) and type 2 diabetes (1373 cases and 4742 controls) and quantitative trait analyses among 5822 individuals. Furthermore, the association of Trp64Arg with type 2 diabetes was examined in a meta-analysis. RESULTS: The Trp64Arg polymorphism was not associated with obesity. However, the Arg-allele was associated with a slightly increased risk of type 2 diabetes (OR1.15 (CI: 1.01-1.31); p=0.04), increased insulin resistance estimated by homeostasis model assessment (p=0.01), higher fasting serum insulin levels (p=0.01), and higher levels of plasma glucose 2-h after glucose ingestion (p=0.02). After sex stratification these associations were only present among women. Furthermore, the Arg-allele was borderline associated with type 2 diabetes in a meta-analysis of the present and 26 previous studies (p=0.06, OR1.27 (CI: 0.99-1.63)) (n=18891). CONCLUSION/INTERPRETATION: Trp64Arg does not confer an increased risk of obesity among Danes. Yet, in the present study of 7605 Danes the variant is associated with type 2 diabetes and quantitative traits related to type 2 diabetes.
AB - AIM/HYPOTHESIS: The functional variant Trp64Arg in the beta(3)-adrenergic receptor has previously been examined for association with obesity and insulin resistance with ambiguous results. For further evaluation the present study examined the impact of the Trp64Arg variant on the pathogenesis of type 2 diabetes and obesity in a relatively large, homogenous study population. METHODS: The Trp64Arg polymorphism was genotyped in 7605 Danish subjects using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Association was examined in case-control studies of obesity (1529 cases and 6049 controls) and type 2 diabetes (1373 cases and 4742 controls) and quantitative trait analyses among 5822 individuals. Furthermore, the association of Trp64Arg with type 2 diabetes was examined in a meta-analysis. RESULTS: The Trp64Arg polymorphism was not associated with obesity. However, the Arg-allele was associated with a slightly increased risk of type 2 diabetes (OR1.15 (CI: 1.01-1.31); p=0.04), increased insulin resistance estimated by homeostasis model assessment (p=0.01), higher fasting serum insulin levels (p=0.01), and higher levels of plasma glucose 2-h after glucose ingestion (p=0.02). After sex stratification these associations were only present among women. Furthermore, the Arg-allele was borderline associated with type 2 diabetes in a meta-analysis of the present and 26 previous studies (p=0.06, OR1.27 (CI: 0.99-1.63)) (n=18891). CONCLUSION/INTERPRETATION: Trp64Arg does not confer an increased risk of obesity among Danes. Yet, in the present study of 7605 Danes the variant is associated with type 2 diabetes and quantitative traits related to type 2 diabetes.
U2 - 10.1016/j.ymgme.2007.12.003
DO - 10.1016/j.ymgme.2007.12.003
M3 - Journal article
C2 - 18249022
SN - 1096-7192
VL - 94
SP - 90
EP - 97
JO - Molecular Genetics and Metabolism
JF - Molecular Genetics and Metabolism
IS - 1
ER -
