| Project/Area Number |
12671715
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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 |
Ophthalmology
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| Research Institution | Kagoshima University |
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Principal Investigator |
OHBA Norio Kagoshima University, Faculty of Medicine, Professor, 医学部, 教授 (50010070)
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| Co-Investigator(Kenkyū-buntansha) |
ISASHIKI Yasushi Kagoshima University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (70168160)
UEHARA Fumiyuki Kagoshima University, Faculty of Medicine, Associate Professor, 医学部, 教授 (30168653)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2001: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2000: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | Age-related maular degeneration / Genetic risk / Polymorphism / Superoxide dismutase / 細胞成長因子 / 発症タスク / スーパーオキスド / 細胞成衰因子 / 外因 / 遺伝的罹病性 / エポキシヒドラ-ゼ |
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| Research Abstract |
To elucidate whether any polymorphic genes for xenobiotic-metabolizing and antioxidant enzymes are associated with the development of exudative age-related macular degeneration. A hospital-based case-control study was performed on a consecutive series of 102 Japanese patients with the exudative form of age-related macular degeneration who were recruited between 1993 and 1998 in the Kagoshima University Hospital. Controlswere 200 systemically healthy individuals who had no senescent ocular disorders and were over 50 years of age. There was no evidence of age-related macular degeneration in the 200 controls. Genomic DNA from peripheral bloods was examined using polymerase chain reaction and defined for the genetic polymorphisms of cytochrome P-450 1A1, glutathione S-transferases, microsomal epoxide hydrolase, and manganese superoxide dismutase. We found a significant association of manganese superoxide dismutase gene polymorphism, valine/alanine polymorphism at the targeting sequence of
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the enzyme, with age-related macular degeneration. The patients had an increased frequency of alanine allele and alanine/aianine genotype. We also observed a weak association of microsomal epoxide hydrolase exon-3 polymorphism with age-related macular degeneration. Cytochrome P-450 1A1, glutathione S-transferases, and microsomal epoxide hydrolase exon-4were polymorphic, but their genotype frequency distributions did not show a statistically significant difference between the patients and controls. The results suggest that manganese superoxide dismutase gene polymorphism is associated with exudative age-related macular degeneration. Microsomal epoxide hydrolase is another enzyme that may be associated with the disease. The exudative form of age-related macular degeneration may have genetic risk factors against oxidative stress and/or effects of xenobiotics. Further association studies in other genes for xenobiotic-metabolizing enzymes are needed to elucidate the environmental-genetic Interaction In the underlying cause of age-related macular degeneration. Less
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