2001 Fiscal Year Final Research Report Summary
Study on associations of novel TNF-α promoter polymorphisms with diabetes and diabetic complications
| Project/Area Number |
12671095
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | Tohoku University |
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Principal Investigator |
SATOH Jo Tohoku University, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (60125565)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Kazuma Tohoku University, University Hospital, Research Associate, 医学部・附属病院, 助手 (60292215)
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| Project Period (FY) |
2000 – 2001
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| Keywords | TNF-α / SNPs / diabetic complications / diabetic neuropathy / diabetic nephropathy / arteriosclerosis |
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| Research Abstract |
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.
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