Abstract
The aim of this meta-analysis was to determine the nature of the association between TNF 238 G/A polymorphism and the risk for T2D. We searched databases updated on January 2009 for all publications on the association between this variation and T2D. Data on genotypes and the numbers of cases and controls were assessed using Review Manager 4.2. Meta-analysis of the overall and specific populations was conducted, and odds ratios (OR) and 95% confidence intervals (95% CI) were calculated in the fixed-effect model. I 2 statistic was calculated to examine heterogeneity, and publication bias was evaluated by Egger test. The overall OR (95% CI) for AA and GA genotypes versus GG genotype for TNF-α-238 was 1.15 (0.92–1.44), which in European and Asian populations were 1.18 (0.92–1.51) and 1.13 (0.62–2.04), respectively. This first meta-analysis of data from the current and published studies did not detect any association between the polymorphism of TNF 238 G/A and risk for T2D.
Abbreviations
- SNP:
-
Single-nucleotide polymorphism
- TNF-α:
-
Tumor necrosis factor-α
- T2D:
-
Type 2 diabetes
- OR:
-
Odds ratio
References
Hotamisligil GS, Shargill NS, Spiegelman BM (1993) Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science 259:87–91
Wilson AG, Symons JA, McDowell TL, McDevitt HO, Duff GW (1997) Effects of a polymorphism in the human tumor necrosis factor alpha promoter on transcriptional activation. Proc Natl Acad Sci USA 94:3195–3199
Hamaguchi K, Kimura A, Seki N et al (2000) Analysis of tumor necrosis factor-alpha promoter polymorphism in type 1 diabetes: HLA-B and -DRB1 alleles are primarily associated with the disease in Japanese. Tissue Antigens 55:10–16
D’Alfonso S, Richiardi PM (1994) A polymorphic variation in a putative regulation box of the TNFA promoter region. Immunogenetics 39:150–154
Fong CL, Siddiqui AH, Mark DF (1994) Identification and characterization of a novel repressor site in the human tumor necrosis factor alpha gene. Nucleic Acids Res 22:1108–1114
Day CP, Grove J, Daly AK, Stewart MW, Avery PJ, Walker M (1998) Tumour necrosis factor-alpha gene promoter polymorphism and decreased insulin resistance. Diabetologia 41:430–434
Sheu WH, Lee WJ, Lin LY, Chang RL, Chen YT (2001) Tumor necrosis factor alpha -238 and -308 polymorphisms do not associate with insulin resistance in hypertensive subjects. Metabolism 50:1447–1451
Valenti L, Fracanzani AL, Dongiovanni P et al (2002) Tumor necrosis factor alpha promoter polymorphisms and insulin resistance in nonalcoholic fatty liver disease. Gastroenterology 122:274–280
Hayakawa T, Nagai Y, Taniguchi M et al (2000) Tumor necrosis factor-beta gene NcoI polymorphism decreases insulin resistance in Japanese men. Metabolism 49:1506–1509
Hamann A, Mantzoros C, Vidal-Puig A, Flier JS (1995) Genetic variability in the TNF-alpha promoter is not associated with type II diabetes mellitus (NIDDM). Biochem Biophys Res Commun 211:833–839
Kim HR, Lee MK, Park AJ (2006) [The −308 and −238 polymorphisms of the TNF-alpha promoter gene in type 2 diabetes mellitus]. Korean J Lab Med 26:58–63
Li H, Groop L, Nilsson A, Weng J, Tuomi T (2003) A combination of human leukocyte antigen DQB1*02 and the tumor necrosis factor alpha promoter G308A polymorphism predisposes to an insulin-deficient phenotype in patients with type 2 diabetes. J Clin Endocrinol Metab 88:2767–2774
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
Santos MJ, Patino GA, Angel BB et al (2006) Association between tumor necrosis factor-alpha promoter polymorphisms and type 2 diabetes and obesity in Chilean elderly women. Rev Med Chil 134:1099–1106
Zeggini E, Groves CJ, Parkinson JR et al (2005) Large-scale studies of the association between variation at the TNF/LTA locus and susceptibility to type 2 diabetes. Diabetologia 48:2013–2017
Chui MH, Papanikolaou Y, Fontaine-Bisson B et al (2007) The TNF-alpha-238G > a single-nucleotide polymorphism protects against memory decline in older adults with type 2 diabetes. Behav Neurosci 121:619–624
Fontaine-Bisson B, Wolever TM, Chiasson JL et al (2007) Tumor necrosis factor alpha -238G>A genotype alters postprandial plasma levels of free fatty acids in obese individuals with type 2 diabetes mellitus. Metabolism 56:649–655
Bonora E, Targher G, Alberiche M et al (2000) Homeostasis model assessment closely mirrors the glucose clamp technique in the assessment of insulin sensitivity: studies in subjects with various degrees of glucose tolerance and insulin sensitivity. Diabetes Care 23:57–63
Aminkeng F, Van Autreve JE, Koeleman BP et al (2007) TNFa microsatellite polymorphism modulates the risk of type 1 diabetes in the Belgian population, independent of HLA-DQ. Hum Immunol 68:690–697
Padovani JC, Pazin-Filho A, Simoes MV, Marin-Neto JA, Zago MA, Franco RF (2000) Gene polymorphisms in the TNF locus and the risk of myocardial infarction. Thromb Res 100:263–269
Molvarec A, Jermendy A, Nagy B et al (2008) Association between tumor necrosis factor (TNF)-alpha G-308A gene polymorphism and preeclampsia complicated by severe fetal growth restriction. Clin Chim Acta 392:52–57
Acknowledgments
We thank Fujun Zhao, Wang Fan, Songtao Li, Baowei Wang, and Yonghan He for their kindly help and discussion. This work was supported by Natural Science Foundation of China (No. 30671756) and China’s 11th Five-Year Scientific and Technical Plan (No. 2006BAD27B05).
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Feng, R., Li, Y., Zhao, D. et al. Lack of association between TNF 238 G/A polymorphism and type 2 diabetes: a meta-analysis. Acta Diabetol 46, 339–343 (2009). https://doi.org/10.1007/s00592-009-0118-3
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DOI: https://doi.org/10.1007/s00592-009-0118-3