Nonen Shinpei, Yamamoto Isamu, Liu Jianmin, Maeda Makiko, Motomura Takashi, Igarashi Tsuyoshi, Fujio Yasushi, Azuma Junichi
Department of Clinical Pharmacology and Pharmacogenomics, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka, Japan.
Biol Pharm Bull. 2008 Feb;31(2):295-8. doi: 10.1248/bpb.31.295.
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.
在脂肪分解过程中,脂肪细胞通过β(1)、β(2)和β(3)肾上腺素能受体(ARs)受儿茶酚胺刺激。到目前为止,已有报道β(2)和β(3) AR多态性与肥胖有关。然而,β(1)AR多态性与肥胖的关系尚未得到评估。在本研究中,我们检测了βAR多态性是否与II型糖尿病患者的肥胖相关表型有关。通过PCR-RFLP对188例II型糖尿病患者的β(1)Ser49Gly、β(1)Arg389Gly、β(2)Arg16Gly、β(2)Gln27Glu和β(3)Trp64Arg多态性进行基因分型。在这些多态性中,发现β(1)Ser49Gly与肥胖有关。携带β(1)Gly49等位基因的受试者的体重指数(BMI)高于携带Ser49/Ser49基因型的受试者(24.7±3.7 vs. 23.4±3.3 kg/m²;p=0.031)。与β(1)Ser49纯合组相比,携带β(1)Gly49等位基因的受试者超重(BMI≥25 kg/m²)的频率更高(42.1% vs. 24.4%,p=0.015)。通过多元线性回归分析,β(1)Ser49Gly多态性与较高的BMI独立相关(p=0.019,β=0.166)。我们的数据表明,β(1)AR中的Gly49等位基因与II型糖尿病患者较高的BMI有关。对II型糖尿病患者进行β(1)Ser49Gly多态性基因分型可能对预测肥胖具有临床益处,从而有助于预防胰岛素抵抗。