Adrenergic beta1 receptor polymorphism (Ser49Gly) is associated with obesity in type II diabetic patients.
In the process of lipolysis, adipocytes are stimulated by catecholamines through beta(1), beta(2), and beta(3) adrenergic receptors (ARs). So far, beta(2) and beta(3) AR polymorphisms have been reported related to obesity. However, the relation of beta(1)AR polymorphisms to obesity has not been evaluated. In the present study, we examined whether betaAR polymorphisms are associated with obesity-related phenotype in type II diabetic patients. Polymorphisms of beta(1)Ser49Gly, beta(1)Arg389Gly, beta(2)Arg16Gly, beta(2)Gln27Glu and beta(3)Trp64Arg were genotyped in 188 type II diabetic patients by PCR-RFLP. Among these polymorphisms, beta(1)Ser49Gly was found to be associated with obesity. Subjects with beta(1)Gly49 allele showed higher body mass index (BMI) than those with Ser49/Ser49 genotype (24.7+/-3.7 vs. 23.4+/-3.3 kg/m(2); p=0.031). Subjects with beta(1)Gly49 allele were more frequently overweight (BMI >or= 25 kg/m(2)) compared with beta(1)Ser49 homozygous group (42.1 vs. 24.4%, p=0.015). By multiple linear regression analysis, beta(1)Ser49Gly polymorphism was independently associated with higher BMI (p=0.019, beta=0.166). Our data indicate that the Gly49 allele in beta(1)AR is associated with higher BMI in type II diabetic patients. Genotyping for beta(1)Ser49Gly polymorphism in type II diabetic patients may have clinical benefit to predict obesity, thereby contributing to the prevention of insulin resistance.
Nonen
Shinpei
S
Department of Clinical Pharmacology and Pharmacogenomics, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka, Japan.
Yamamoto
Isamu
I
Liu
Jianmin
J
Maeda
Makiko
M
Motomura
Takashi
T
Igarashi
Tsuyoshi
T
Fujio
Yasushi
Y
Azuma
Junichi
J
D000368:Aged; D004247:DNA / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics*; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics / Q000502:physiology; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics*; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics; D022702:Receptors, Adrenergic, beta-3 / Q000235:genetics; D012044:Regression Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D022702:Receptors, Adrenergic, beta-3; D004247:DNA