Association of TNF-alpha gene promoter C-857T polymorphism with higher serum LDL cholesterol levels and carotid plaque formation in Japanese patients with type 2 diabetes

Tohoku J Exp Med. 2007 Mar;211(3):251-8. doi: 10.1620/tjem.211.251.


Little has been known about the role of tumor necrosis factor-alpha (TNF-alpha) gene polymorphisms in metabolic syndrome and atherosclerosis in type 2 diabetes, although TNF-alpha was reported to be involved in these conditions. We examined the association of TNF-alpha gene promoter polymorphisms, G-238A, G-308A, C-857T, C-863A, and T-1031C, with metabolic syndrome and surrogate markers of atherosclerosis in Japanese patients with type 2 diabetes. DNA was obtained from 162 patients and TNF-alpha gene promoter polymorphisms determined by direct sequencing. Allelic frequency of -238A, -308A, -857T, -863A, and -1031C was 0.6%, 2.2%, 11.1%, 16.7%, and 15.7%, respectively. Association of the gene polymorphisms with a number of variables, because of their high frequency, was analyzed in the latter 3 polymorphisms. There were no significant differences in components of metabolic syndrome and variables affecting atherosclerosis, except in case of serum low-density-lipoprotein cholesterol (LDL-C) (111+/-33 vs 125+/-39 mg/dl, p<0.05) between -857C/C and -857(C/T+T/T). In contrast, no significant differences were found in these markers between -863C/C and -863(C/A+A/A) and between -1031T/T and -1031(T/C+C/C). Furthermore, 87% of the patients with -857(C/T+T/T) and 64% with -857C/C had carotid plaques (p<0.05). There was no difference in proportion of patients treated with medications such as statins, fibrates, oral hypoglycemic agents, insulin, or antihypertensive drugs between -857C/C and -857(C/T+T/T). These data imply that TNF-alpha gene polymorphism (C-857T) is likely associated with higher serum LDL-C levels and carotid plaque formation in Japanese patients with type 2 diabetes.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Carotid Artery Diseases / diagnostic imaging*
  • Carotid Artery Diseases / etiology
  • Cholesterol, LDL / blood*
  • DNA Primers
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetes Mellitus, Type 2 / pathology
  • Female
  • Humans
  • Japan
  • Male
  • Metabolic Syndrome / etiology
  • Metabolic Syndrome / genetics*
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics*
  • Promoter Regions, Genetic / genetics*
  • Sequence Analysis, DNA
  • Tumor Necrosis Factor-alpha / genetics*
  • Ultrasonography


  • Cholesterol, LDL
  • DNA Primers
  • Tumor Necrosis Factor-alpha