Impact of genetic polymorphisms of leptin and TNF-alpha on rosiglitazone response in Chinese patients with type 2 diabetes.
BACKGROUND
Leptin and tumor necrosis factor-alpha (TNF-alpha) play important role in homeostasis and insulin resistance in the treatment of Type 2 diabetes (T2DM). The aims of the present study were to investigate the association between leptin G-2548A and TNF-alpha G-308A polymorphisms and rosiglitazone response in T2DM patients.


METHODS
245 patients with T2D and 122 health volunteers were enrolled to identify leptin G-2548A and TNF-alpha G-308A genotypes by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Forty-two T2D patients with different leptin G-2548A and TNF-alpha G-308A genotypes received orally rosiglitazone as a single-agent therapy (4 mg day(-1) p.o.) for 12 weeks. Serum triglyceride (TG), fasting plasma glucose (FPG), postprandial plasma glucose (PPG), fasting serum insulin (FINs), glycated hemoglobin (HbAlc), postprandial serum insulin (PINS), homeostasis model assessment for insulin resistance (HOMA-IR), low-density lipoprotein-cholesterol (LDL-c), and high-density lipoprotein-cholesterol (HDL-c) were determined before and after rosiglitazone treatment.


RESULTS
A significant association between the variation of G-2548A allele with body mass index (BMI), serum leptin levels and FPG was observed in T2DM patients. Moreover, patients with G allele of leptin G-2548A had lower BMI and serum leptin concertration as well as bigger FPG than that in AA genotypes (P < 0.05). Moreover, we found an enhanced rosiglitazone effect in patients with AA genotype of leptin G-2548A on FINS and PINS compared with GG+GA genotype (P < 0.05). Finally, our results showed an attenuated rosiglitazone effect in patients with GA+AA genotype of TNF-alpha G-308A on FINS compared with GG genotype (P < 0.05).


CONCLUSIONS
These data suggest there were not significantly differences in the frequencies of leptin G-2548A and TNF-alpha G-308A between patients with T2DM and health control. TNF-alpha G-308A polymorphism might be associated with the therapeutic efficacy of rosiglitazone in T2DM patients.
Liu
Hai-Ling
HL
Institute of Clinical Pharmacology, Key Laboratory of Pharmacogenetics in Hunan Province, Central South University, Changsha, Hunan 410078, People's Republic of China.
Lin
Yang-Gen
YG
Wu
Jing
J
Sun
Hong
H
Gong
Zhi-Cheng
ZC
Hu
Ping-Cheng
PC
Yin
Ji-Ye
JY
Zhang
Wei
W
Wang
Dan
D
Zhou
Hong-Hao
HH
Liu
Zhao-Qian
ZQ
D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000032:analysis; D002681:China; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D020738:Leptin; D045162:Thiazolidinediones; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D000077154:Rosiglitazone