权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

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

新型TNF-α启动子多态性与糖尿病及糖尿病并发症的相关性研究

基本信息

批准号：
12671095
负责人：
SATOH Jo
金额：
$ 2.24万
依托单位：
Tohoku University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671095/
关键词：
TNF-α SNPs diabetic complications diabetic neuropathy diabetic nephropathy arteriosclerosis

项目摘要

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.

TNF-α 可能在糖尿病性多发性神经病中发挥作用。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 与正中神经中 F 波潜伏期和运动神经传导速度 (MNCV) 的关联，作为 2 型糖尿病多发性神经病的标志物。DNA 取自 94 名日本患者直接测序测定2型糖尿病患者TNF-α启动子多态性，正中神经测定最小F波潜伏期和MNCV。-857C/T、-863C/A或-1031T/C基因型分布处于Hardy-Weinberg平衡状态。 -863C/A和-1031T/C多态性存在连锁不平衡，而-857C/T和-863C/A或-1031T/C则不存在连锁不平衡。根据各多态性将2型糖尿病患者分为两组； -857C/C (N=61) 和-857(C/T+T/T) (N=33)，以及-863C/C 或-1031T/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)之间外，背景因素没有差异（91.9±43.3 vs. 134±61.7 mg/dl，P<0.001）。 -857(C/T+T/T)组正中神经F波潜伏期较-857C/C组显着延长(29.0±6.2 vs. 26.3±3.5毫秒，P<0.01)，但MNCV无差异。 -863 或 -1031 TNF-α 多态性与 F 波潜伏期或 MNCV 没有关联。这些数据表明 TNF-α 高产基因型与所研究的患者糖尿病性多发性神经病早期阶段的运动神经传导延迟相关，并且可能暗示 TNF-α 在糖尿病性多发性神经病的发病机制中的作用。