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

TNF-α可能在糖尿病多发神经病变中起作用。在这项研究中，我们分析了新型TNF-α启动子基因多态性C(-857)T、C(-863)A或T(-1031)C与正中神经f波潜伏期和运动神经传导速度（MNCV）作为2型糖尿病多发性神经病变标志物的关系。从94名日本2型糖尿病患者中获得DNA，通过直接测序确定TNF-α启动子多态性，并测量正中神经的最小f波潜伏期和MNCV。-857C/T、-863C/A或-1031T/C基因型分布符合Hardy-Weinberg平衡。-863C/A和-1031T/C多态性为连锁不平衡，-857C/T和-863C/A或-1031T/C多态性不为连锁不平衡。2型糖尿病患者按多态性分为两组；-857 C / C (N = 61)和-857 (C / T + T / T) (N = 33),和-1031年-863 C / C或T / T (N = 64)和-863 (C / A + A / A)或-1031 (T / C + C / C) (N = 30)。除血清甘油三酯水平在-857C/C和-857（C/T+T/T）之间（91.9±43.3 vs 134±61.7 mg/dl， P<0.001）外，背景因素无差异。正中神经f波潜伏期在-857（C/T+T/T）组明显长于-857C/C组（29.0±6.2 vs. 26.3±3.5 ms， P<0.01），但在MNCV组间无显著差异。-863或-1031 TNF-α多态性与f波潜伏期或MNCV无关。这些数据表明，TNF-α高产生基因型与糖尿病多发性神经病变早期运动神经传导延迟有关，可能暗示TNF-α在糖尿病多发性神经病变的发病机制中起作用。

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.