The Arg16Gly polymorphism of human β2-adrenoreceptor is associated with type 2 diabetes in Taiwanese people

OBJECTIVE The significance of the association of amino terminal polymorphisms in beta2-adrenoreceptor (ADRB2) with obesity and type 2 diabetes is controversial and differs among ethnic groups. In this study, the association of ADRB2 with risk and age of onset of type 2 diabetes has been examined in a Taiwanese population. DESIGN The study design is a case-control study to investigate the impact of the two amino acid polymorphisms in ADRB2. PATIENTS AND MEASUREMENTS This study includes 130 patients with type 2 diabetes [female : male = 1 : 1, age: 52.4 +/- 10.0 years; body mass index (BMI): 24.2 +/- 2.9 kg/m(2); mean +/- SD] and 130 controlled subjects matched for gender, age and BMI with normal glucose tolerance (female : male = 1 : 1, age: 51.7 +/- 10.6 years; BMI: 23.9 +/- 2.7 kg/m(2)). The Arg16Gly and Gln27Glu polymorphisms of ADRB2 were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assays. The genotypic and allelic frequencies between two groups were compared and the relationship between the genotypes and clinical phenotypes was examined. RESULTS A difference in genotypic frequency in the Arg16Gly polymorphism was noted between groups in this gender-, age- and BMI-matched case-control study (P = 0.039). Multivariate regression analysis revealed that the Arg16Gly polymorphism was the only independent factor for development of type 2 diabetes (P = 0.021). In addition, we utilized the log-rank test to compare the differences in age of onset between wildtype and nonwild-type polymorphisms. The Arg16Gly polymorphism was independently associated with age of onset in type 2 diabetes (P = 0.017). There was no difference in the Gln27Glu polymorphism between diabetic and control groups in this study. CONCLUSIONS In a Taiwanese population, homozygosity of Arg16 in the ADRB2 gene was associated with a higher frequency (odds ratio 1.87, 95% confidence interval 1.34-2.40) for development of type 2 diabetes. Moreover, this polymorphism was also associated with an earlier onset of type 2 diabetes. However, the Glu27Gln polymorphism had no impact on either BMI or type 2 diabetes in a Taiwanese population.