Effects of UCP2 –866 G/A and ADRB3 Trp64Arg on rosiglitazone response in Chinese patients with Type 2 diabetes
Authors: Yang Min , Huang Qiong , Wu Jing , Yin Ji‐Ye , Sun Hong , Liu Hai‐Ling , Zhou Hong‐Hao , Liu Zhao‐Qian 
Published: May 2009

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Rosiglitazone is one of the thiazolidinedione medicines that is widely used in patients with Type 2 diabetes (T2DM); it acts by activation of peroxisome proliferator‐activated receptor‐γ.

• There are no reports on the influence of genetic variations of UCP2 and ADRB3 on rosiglitazone response in Chinese T2DM patients.

• The current study was designed to evaluate the relationship between the genetic polymorphisms of UCP2 –866G/A and ADRB3 Trp64Arg with susceptibility to T2DM development and the therapeutic efficacy of multiple‐dose rosiglitazone in Chinese patients with T2DM.

WHAT THIS STUDY ADDS

• The genetic polymorphisms of UCP2 –866G/A and ADRB3 Trp64Arg are associated with the therapeutic efficacy of multiple‐dose rosiglitazone in Chinese T2DM patients.

AIMS

The aim of this study was to explore the impact of UCP2 and ADRB3 genetic polymorphisms on the therapeutic efficacy of rosiglitazone in Chinese Type 2 diabetes (T2DM) patients.

METHODS

A total of 199 T2DM patients and 155 healthy volunteers were enrolled to identify UCP2 –866 G/A genotypes, and 273 T2DM patients and 166 controls were genotyped for Trp64Arg of ADRB3 by polymerase chain reaction‐restriction fragment length polymorphism assay. Nine patients with GG genotype and 27 with GA+AA genotype of UCP2 –866 G/A, 11 with Trp64Trp genotype and 25 with Trp64Arg genotype of ADRB3 received oral rosiglitazone as a single‐agent therapy (4 mg day−1) for 12 weeks. Serum fasting plasma glucose, postprandial plasma glucose, glycated haemoglobin (HbA1c), fasting serum insulin, postprandial serum insulin (PINS), triglycerol (TG), cholesterol, homeostasis model assessment for insulin resistance, leptin and adiponectin in all T2DM patients were determined before and after rosiglitazone treatment.

RESULTS

There were no differences in allele frequency of either ADRB3 Trp64Arg or UCP2 –866 G/A between T2DM patients and control subjects. The A allele carriers of UCP2 in the T2DM patients had significantly lower PINS (61.5 ± 34.3 vs. 41.6 ± 28.7 mU l−1, P < 0.01) (37.57, 59.16 vs. 34.82, 49.39) and low‐density lipoprotein (LDL)‐cholesterol compared with GG genotypes (3.4 ± 1.1 vs. 2.7 ± 1.1 mmol l−1, P < 0.05) (2.64, 3.52 vs. 2.66, 3.15). After rosiglitazone treatment for 12 consecutive weeks, we found that A allele carriers of UCP2 in the T2DM patients had smaller attenuated PINS (−3.82 ± 13.2 vs.−42.1 ± 30.7 mU l−1, P < 0.01) (9.45, 51.31 vs. 0.48, 11.88) and greater attenuated HbA1c (−1.85 ± 1.62 vs.−0.61 ± 0.80, P < 0.05) (0.14, 1.37 vs. 1.10, 2.38) compared with GG genotypes, and ADRB3 Trp64Arg had greater attenuated serum TG (−3.88 ± 2.77 vs.−0.24 ± 1.16 mmol l−1, P < 0.05) (−0.19, 2.74 vs. 1.19, 1.45) and smaller attenuated LDL‐cholesterol (1.08 ± 1.36 vs.−0.36 ± 0.99, P < 0.01) (−1.26, 0.78 vs.−1.26, 0.79) as well as reduced enhanced adiponectin (1.57 ± 1.10 vs. 3.15 ± 2.12 mmol l−1, P < 0.05) (1.68, 4.08 vs.−9.18, 11.40) compared with ADRB3 Trp64Trp.

CONCLUSION

UCP2 –866 G/A and ADRB3 Trp64Arg polymorphisms are associated with the therapeutic efficacy of multiple‐dose rosiglitazone in Chinese T2DM patients.