The association of adiponectin allele 45T/G and -11377C/G polymorphisms with Type 2 diabetes and rosiglitazone response in Chinese patients.
BACKGROUND
Rosiglitazone is able to increase serum adiponectin levels significantly in Type 2 diabetic patients. :The role of genetic factors that determine the marked interindividual variability in glucose-lowering efficacy of rosiglitazone in Chinese patients is not known. The current study was designed to evaluate the impact of the adiponectin common allele 45T/G and -11377C/G polymorphisms on the response to rosiglitazone monotherapy in Chinese patients with Type 2 diabetes (T2D).


CONCLUSIONS
The genetic polymorphisms of adiponectin alleles 45T/G and -11377C/G as well as their common diplotypes are significantly associated with an attenuated fasting plasma glucose, postprandial plasma glucose and homeostasis model assessment for insulin resistance as well as an enhanced adiponectin concentration in Chinese patients with T2D after rosiglitazone treatment. AIMS The aim of the present study was to evaluate the impact of adiponectin allele T45G and C-11377G genetic polymorphisms on efficacy of rosiglitazone in Chinese patients with type 2 diabetes (T2D).


METHODS
Patients with T2D (n = 255) and 120 healthy volunteers were enrolled to identify 45T/G and -11377C/G genotypes by polymerase chain reaction-restriction fragment length polymorphism assay. Forty-two T2D patients with different 45T/G or -11377C/G genotypes received orally rosiglitazone as a single-dose therapy (4 mg day-1 p.o.) for 12 weeks. Serum triglyceride, fasting plasma glucose (FPG), postprandial plasma glucose (PPG), glycated hemoglobin, fasting serum insulin, postprandial serum insulin, total cholesterol, homeostasis model assessment for insulin resistance (HOMA-IR), low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol (HDL-c) and adiponectin concentration were determined before and after rosiglitazone treatment.


RESULTS
We showed an attenuated rosiglitazone effect in patients with -11377CG+GG heterozygote genotype on FPG, PPG, HOMA-IR compared with -11377CC homozygote genotype. However, we found an enhanced rosiglitazone effect on serum adiponectin concentration in patients with -11377CC homozygote genotype compared with -11377CG+GG heterozygote genotype (P = 0.000) and in patients with 45TG + GG heterozygote genotype compared with 45TT homozygote genotype (P = 0.018). Finally, our results showed that there was an enhanced effect in patients with -11377/45 CGTT diplotype compared with other discovered diplotypes on FPG (P = 0.001) and PPG (P = 0.003) after rosiglitazone treatment.


CONCLUSIONS
These data suggest that the adiponectin allele 45T/G and -11377C/G polymorphisms are significantly associated with the therapeutic efficacy of multiple-dose rosiglitazone in Chinese patients with T2D.
Sun
Hong
H
Department of Pharmacy, Fujian Provincal Hospital, Fuzhou, China. sunhong7777@126.com
Gong
Zhi-Cheng
ZC
Yin
Ji-Ye
JY
Liu
Hai-Ling
HL
Liu
Ying-Zi
YZ
Guo
Zhi-Wei
ZW
Zhou
Hong-Hao
HH
Wu
Jing
J
Liu
Zhao-Qian
ZQ
D052242:Adiponectin / Q000097:blood / Q000235:genetics*; D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000493:pharmacokinetics*
D052242:Adiponectin; D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077154:Rosiglitazone