| Project/Area Number |
11671032
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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 |
Kidney internal medicine
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| Research Institution | NIIGATA UNIVERSITY |
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Principal Investigator |
NARITA Ichiei NIIGATA UNIVERSITY Graduate School of Medical and Dental Sciences, Associate Professor, 大学院・医歯学総合研究科, 助教授 (20272817)
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| Co-Investigator(Kenkyū-buntansha) |
UENO Mitsuhiro Medical Hospital, Lecturer, 医学部附属病院, 講師 (90260546)
NISHI Shinichi Medical Hospital, Associate Professor, 医学部附属病院, 助教授 (70251808)
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| Project Period (FY) |
1999 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2002: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 2001: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | IgA nephropathy / Genetic polymorphism / Hypertension / Angiotensinogen / Fcα receptor / Polymeric immunoglobulin receptor / Uteroglobin / α-adducin / Polymeric immunoglobulin receptor / Fcα receptor / Uteroglobin / α-Adducin / アンジオテンシンノーゲン / IFN-γ / gene polymorphism / TGF-β1 / MCP-1 / Renin-angiotensin system / STAT1 |
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| Research Abstract |
Immunoglobulin A nephropathy (IgAN), one of the most prevalent forms of primary glomerulonephritis, is the major course of end-stage renal failure. The disease has a variable clinical course and one third of the patients with IgAN progress to end stage renal disease (ESRD) within 10-20 years of the onset. The pathogenesis of mesangial IgA deposition and the mechanism of inter-individual differences in the rate of disease progression are still unclear, although an accumulating amount of evidence suggests that genetic factors determine the susceptibility to developing IgAN as well as to the progression of renal dysfunction. In this study, we have investigated genetic backgrounds, which are implicated in the development and progression of IgA nephropathy.
We surveyed possible associations between the development of IgAN and genetic polymorphisms of IgA receptors, such as polymeric immunoglobulin receptor (plgR), Fcα receptor (FcαR), and asialoglycoprotein receptor (AGPR). We have reported
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that (1) the genotype distribution of plgR was significantly different between the patients with IgAN and those without IgAN and that (2) the genetic polymorphisms in the promoter and 5' UTR region of FcαR were not associated with a risk of IgAN.
In order to clarify mechanisms of the disease progression, significances of genetic polymorphisms, including those of renin-angiotensin system, Sa, α-adducin, TGF-β1 , MCP-1, and etc, in progression to ESRD were analyzed in patients with biopsy proven IgAN by using multivariate Cox proportional hazard regression model. We have reported that a C allele of A-20C polymorphism in Angiotensinogen gene was an independent risk factor for ESRD. We have also found that uteroglobin gene polymorphism had an implication for the disease progression in IgAN patients with hypertension and heavy proteinuria.
We have started a further investigation to explore the disease-causing gene by using genome-wide linkage and association analysis with microsattelite markers and single nucleotide polymorphisms. Less
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