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Impact of genetic polymorphisms of leptin and TNF-α on rosiglitazone response in Chinese patients with type 2 diabetes

European Journal of Clinical Pharmacology volume 64, Article number: 663 (2008) Cite this article

Abstract

Background

Leptin and tumor necrosis factor-α (TNF-α) 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-α G-308A polymorphisms and rosiglitazone response in T2DM patients.

Materials

245 patients with T2D and 122 health volunteers were enrolled to identify leptin G-2548A and TNF-α 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-α 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-α 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-α G-308A between patients with T2DM and health control. TNF-α G-308A polymorphism might be associated with the therapeutic efficacy of rosiglitazone in T2DM patients.

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Abbreviations

PCR-RFLP:

polymerase chain reaction-restriction fragment length polymorphism

FPG:

fasting plasma glucose

PPG:

postprandial plasma glucose

HbAlc:

glycated hemoglobin

FINS:

fasting serum insulin

PINS:

postprandial serum insulin

HOMA-IR:

homeostasis model assessment for insulin resistance

ANOVA:

analysis of variance

LDL-c:

low density lipoprotein-cholesterol

TNF-α:

tumor necrosis factor-α

T2DM:

Type 2 diabetes

BMI:

body mass index

CHO:

cholesterol

TG:

triglycerol

HDL-c:

high density lipoprotein-cholesterol

DV:

differential value (before and after administration)

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Acknowledgement

The work was supported by grants from the National Natural Science Foundation of China, No 30070880 and No 30572230, and the Supported Program for New Century Excellent Talents in University sponsored by Ministry of Education of China, No NCET-04-0749.

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Affiliations

  1. Institute of Clinical Pharmacology, Key Laboratory of Pharmacogenetics in Hunan Province, Central South University, Changsha, Hunan, 410078, People’s Republic of China

    Hai-Ling Liu, Hong Sun, Zhi-Cheng Gong, Ping-Cheng Hu, Ji-Ye Yin, Wei Zhang, Dan Wang, Hong-Hao Zhou & Zhao-Qian Liu

  2. Department of Cardiovascular Internal Medicine, Xiang-Ya Hospital, Central South University, Changsha, Hunan, 410008, People’s Republic of China

    Yang-Gen Lin

  3. Department of Endocrinology, Xiang-Ya Hospital, Central South University, Changsha, Hunan, 410008, People’s Republic of China

    Jing Wu

Authors
  1. Hai-Ling Liu
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  2. Yang-Gen Lin
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  3. Jing Wu
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  4. Hong Sun
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  5. Zhi-Cheng Gong
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  6. Ping-Cheng Hu
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  7. Ji-Ye Yin
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  8. Wei Zhang
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  9. Dan Wang
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  10. Hong-Hao Zhou
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  11. Zhao-Qian Liu
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Corresponding author

Correspondence to Zhao-Qian Liu.

Additional information

This project was supported by the National Natural Science Foundation of China grant, No 30572230, and the Supported Program for New Century Excellent Talents in University sponsored by Ministry of Education of China, No. NCET-04-0749.

Yang-Gen Lin and Jing-Wu these authors have contributed equally.

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Liu, HL., Lin, YG., Wu, J. et al. Impact of genetic polymorphisms of leptin and TNF-α on rosiglitazone response in Chinese patients with type 2 diabetes. Eur J Clin Pharmacol 64, 663 (2008). https://doi.org/10.1007/s00228-008-0483-9

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  • DOI: https://doi.org/10.1007/s00228-008-0483-9

Keywords

  • Leptin
  • TNF-α
  • Genetic polymorphism
  • Rosiglitazone
  • Type 2 diabetes