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

Abstract

Little has been known about the role of tumor necrosis factor-α (TNF-α) gene polymorphisms in metabolic syndrome and atherosclerosis in type 2 diabetes, although TNF-α was reported to be involved in these conditions. We examined the association of TNF-α 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-α 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/ d1, 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 -103-IT/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 antihypertensiYe drugs between -857C/C and -857(C/T + T/T). These data imply that TNF-α gene polymorphism (C-857T) is likely associated with higher serum LDL-C levels and carotid plaque formation in Japanese patients with type 2 diabetes. © 2007 Tohoku University Medical Press.