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.
Similar content being viewed by others
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)
References
Grinberg A, Park KW (2005) Nuclear Peroxisom Proliferator Activated Receptors and Thiazolidinediones. Int Anesthesiol Clin 43(2):1–21
Berger JP, Akiyama TE, Meinke PT (2005) PPARs: therapeutic targets for metabolic disease. Trends Pharmacol Sci 26(5):244–252
Hammarstedt A, Andersson CX, Sopasakis VR, Smith U (2005) The effect of PPARg ligands on the adipose tissue in insulin resistance. Prostaglandins 73:65–75
Jazet IM, Pijl H, Meinders AE (2003) Adipose tissue as an endocrine organ: impact on insulin resistance. The Netherlands J Med 61(6):194–213
Yildiz BO, Haznedaroglu IC (2006) Rethinking leptin and insulin action: Therapeutic opportunities for diabetes. Int J Biochem Cell Biol 38:820–830
Toyoshima Y, Gavrilova O, Yakar S, Jou W, Pack S, Asghar Z, Wheeler MB, LeRoith D (2005) Leptin Improves Insulin Resistance and Hyperglycemia in a Mouse Model of Type 2 Diabetes. Endocrinology 146(9):4024–4035
Wu J, Lei MX, Chen HL, Sun ZX (2004) Effects of rosiglitazone on serum leptin and insulin resistance in patients with Type 2 diabetes. Zhong Nan Da Xue Xue Bao Yi Xue Ban 29(6):623–629
van der Lende T, te Pas MFW, Veerkamp RF, Liefers SC (2005) Leptin Gene Polymorphisms and Their Phenotypic Associations. Vitam Horm 71(5):373–405
Hoffstedt J, Eriksson P, Mottagui-Tabar S, Arner P (2002) A Polymorphism in the Leptin Promoter Region(−2548 G/A) Influences Gene Expression and Adipose Tissue Secretion of Leptin. Horm Metab Res 34:355–359
Yiannakouris N, Melistas L, Yannakoulia M, Mungal K, Mantzoros CS (2003) The−2548G/A polymorphism in the human leptin gene promoter region is associated with plasma free leptin levels; interaction with adiposity and gender in healthy subjects. Hormones 2(4):229–236
Wang TN, Huang MC, Chang WT, Ko SAM, Tsai EM, Liu CH, Lee CH, Ko YC (2006) G-2548A Polymorphism of the Leptin Gene Is Correlated with Extreme Obesity in Taiwanese Aborigines. Obesity 14(2):183–188
Ren W, Zhang SH, Wu J, Ni YX (2004) Polymorphism of the leptin gene promoter in pedigrees of type 2 diabetes mellitus in Chongqing, China. Chin Med J 117(4):558–561
Stephen EB (2004) The Role of TNF-a in Insulin Resistance. Endocrine 23(2):177–182
Diehl AM (2004) Tumor necrosis factor and its potential role in insulin resistance and nonalcoholic fatty liver disease. Clin Liver Dis 8:619–638
Pihlajamaki J, Ylinen M, Karhapa P, Vauhkonen I, Laakso M (2003) The Effect of the G-308A Allele of the TNF-α Gene on Insulin Action Is Dependent on Obesity. Obes Res 11(7):912–918
Furuta M, Yano Y, Ito K, Gabazza EC, Katsuki A, Tanaka T, Ohtake K, Hirata N, Hori Y, Araki-Sasaki R, Sumida Y, Adachi Y (2002) Relationship of the tumor necrosis factor-alpha -308A/G promoter polymorphism with insulin sensitivity and abdominal fat distribution in Japanese patients with type 2 diabetes mellitus. Diabetes Res Clin Pract 56:141–145
Ko GT, Lee SC, Pu YB, Ng MC, So WY, Thomas N, Chan WB, Cockram CS, Chan JC (2003) Tumor necrosis factor-alpha promoter gene polymorphism at −308 (genotype AA) in Chinese subjects with Type 2 diabetes. Diabet Med 20:167–168
Shiau MY, Wu CY, Huang CN, Hu SW, Lin SJ, Chang YH (2003) TNF-alpha polymorphisms and type 2 diabetes mellitus in Taiwanese patients. Tissue Antigens 61:393–397
Sookoian SC, Lez CG, Pirola CJ (2005) Meta-analysis on the G-308A Tumor Necrosis Factora Gene Variant and Phenotypes Associated with the Metabolic Syndrome. Obes Res 13(12):2122–2133
Kim YM, Cha BS, Kim DJ, Choi SH, Kim SK, Ahn CW, Lim SK, Kim KR, Huh KB, Lee HC (2005) Predictive clinical parameters for therapeutic efficacy of rosiglitazone in Korean type 2 diabetes mellitus. Diabetes Res Clin Pract 67:43–52
Kang ES, Park SY, Kim HJ, Kim CS, Ahn CW, Cha BS, Lim SK, Nam CM, Lee HC (2005) Effects of Pro12Ala polymorphism of peroxisome proliferator-activated receptor gamma2 gene on rosiglitazone response in type 2 diabetes. Clin Pharmacol Ther 78(2):202–208
Kang ES, Park SY, Kim HJ, Kim CS, Ahn CW, Cha BS, Lim SK, Nam CM, Lee HC (2005) The influence of adiponectin gene polymorphism on the rosiglitazone response in patients with type 2 diabetes. Diabetes Care 28(5):1139–1144
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.
Author information
Authors and Affiliations
Corresponding author
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.
Rights and permissions
About this article
Cite this article
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, 663–671 (2008). https://doi.org/10.1007/s00228-008-0483-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00228-008-0483-9