Study on associations of novel TNF-α promoter polymorphisms with diabetes and diabetic complications

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It has been implicated that TNF-α may play a role in diabetic polyneuropathy. In this study, we analyzed an association of novel TNF-α promoter gene polymorphisms, C(-857)T, C(-863)A or T(-1031)C, with F-wave latency and motor nerve conduction velocity (MNCV) in the median nerve as markers of diabetic polyneuropathy in type 2 diabetes mellitus.DNA was obtained from 94 Japanese patients with type 2 diabetes and TNF-α promoter polymorphisms were determined by direct sequencing, Minimal F-wave latency and MNCV were measured with the median nerve.The genotype distributions of -857C/T and -863C/A or -1031T/C were in Hardy-Weinberg equilibrium. The -863C/A and -1031T/C polymorphisms were in linkage disequilibrium, while the -857C/T and -863C/A or -1031T/C were not. The patients with type 2 diabetes were divided into two groups according to each polymorphism ; -857C/C (N=61) and -857(C/T+T/T) (N=33), and -863C/C or -1031T/T (N=64) and -863(C/A+A/A) or -1031(T/C+C/C) (N=30). There was no difference in background factors, except for serum triglyceride levels between -857C/C and -857(C/T+T/T) (91.9±43.3 vs. 134±61.7 mg/dl, P<0.001). F-wave latency of the median nerve was significantly prolonged in -857(C/T+T/T) than that in -857C/C (29.0±6.2 vs. 26.3±3.5 milliseconds, P<0.01), although there was no difference in MNCV. There was no association of -863 or -1031 TNF-α polymorphisms with F-wave latency or MNCV.These data indicate that a TNF-α high producer genotype is associated with delay of motor nerve conduction in an early stage of diabetic polyneuropathy in the patients studied, and may imply a role of TNF-α in the pathogenesis of diabetic polyneuropathy.