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.
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.
Yamashina
Mitsuhiro
M
Department of Diabetes and Metabolism, Iwate Medical University, Morioka, Japan. yamashina0512@yahoo.co.jp
Kaneko
Yoshihiro
Y
Maesawa
Chihaya
C
Kajiwara
Takashi
T
Ishii
Mototsugu
M
Fujiwara
Fumikado
F
Taneichi
Haruhito
H
Takebe
Noriko
N
Ishida
Wataru
W
Takahashi
Kazuma
K
Masuda
Tomoyuki
T
Satoh
Jo
J
D000368:Aged; D002340:Carotid Artery Diseases / Q000000981:diagnostic imaging* / Q000209:etiology; D008078:Cholesterol, LDL / Q000097:blood*; D017931:DNA Primers; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D024821:Metabolic Syndrome / Q000209:etiology / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D017422:Sequence Analysis, DNA; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D014463:Ultrasonography
D008078:Cholesterol, LDL; D017931:DNA Primers; D014409:Tumor Necrosis Factor-alpha