[The effect of single nucleotide polymorphism SNP + 45 of the adiponectin gene on the rosiglitazone maleate response in patients with type 2 diabetes].
OBJECTIVE
To investigate the effect of single nucleotide polymorphism (SNP) + 45 of the adiponectin (ADIPOQ) gene on the response to therapy with rosiglitazone maleate in patients with type 2 diabetes.


METHODS
A total of 103 newly diagnosed type 2 diabetes patients without taking any drug were enrolled and treated with rosiglitazone maleate (4 or 8 mg/d) for 24 weeks. On scheduled time phenotype measured were height, weight, waist, hip; blood pressure; HbA1c; plasma glucose level, serum insulin level, serum proinsulin level of blood obtained at 0, 2, 4 and 6 minute during arginine stimulation test; serum lipid level including total cholesterol, triglyceride, high-density and low-density lipoprotein cholesterol. Response to the rosiglitazone maleate therapy was defined by both a > or = 20% decrease in fasting plasma glucose and a > or = 15% decrease in HbA1c values after 24 weeks of rosiglitazone maleate treatment. All patients were genotyped for the ADIPOQ SNP + 45 by PCR-RFLP.


RESULTS
(1) Of the 103 patients, the frequencies of TT, TG and GG genotypes of ADIPOQ SNP + 45 were 0.55, 0.36 and 0.09 respectively. The T allele frequency and G allele frequency were 0.73 and 0.27 respectively. (2) There was a significant difference in the response rate to rosiglitazone maleate treatment between the TT genotype and the TG + GG genotype (P = 0.0295). Response rate of the TG + GG genotype (56.41%) was higher than that of the TT genotype (33.93%). Furthermore, multivariate Logistic regression analysis revealed that SNP + 45 of ADIPOQ gene and HbA1c were the independent risk factors for rosiglitazone maleate treatment response. (3) After 24 weeks of treatment period, the FPG, 2hPG, HbA1c and HOMA-IR were significantly decreased in comparison with pre-treatment in both genotype groups. (4) The change in the clinical parameters after 24 weeks of treatment period showed no significant difference between the SNP + 45 of ADIPOQ gene.


CONCLUSIONS
SNP + 45 of ADIPOQ gene is associated with the response rate to rosiglitazone maleate treatment in patients with type 2 diabetes and may be the major determinant of response rate. The response rate of the TG + GG genotype is higher than that of the TT genotype.
Zhang
Hua
H
Shanghai Clinical Center for Diabetes, Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Jiaotong University Affiliated No. 6 People's Hospital, Shanghai 200233, China.
Jia
Wei-ping
WP
Hu
Cheng
C
Zhang
Rong
R
Wang
Cong-rong
CR
Bao
Yu-qian
YQ
Lu
Jun-Xi
JX
Xu
Jing
J
Xiang
Kun-san
KS
D052242:Adiponectin / Q000235:genetics*; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency; D005838:Genotype; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use*; D016896:Treatment Outcome
D052242:Adiponectin; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D008055:Lipids; D000077154:Rosiglitazone; D045162:Thiazolidinediones