Genetic risk of age-related macular Degeneration

阐明外源代谢和抗氧化酶的多态性基因是否与渗出性年龄相关性黄斑变性的发生有关。一项以医院为基础的病例对照研究对1993年至1998年间在鹿儿岛大学医院招募的102名患有渗出型老年性黄斑变性的日本患者进行了连续的系列研究。对照组为200名50岁以上、无衰老性眼部疾病的全身健康个体。在200名对照组中，没有证据表明黄斑变性与年龄有关。采用聚合酶链反应检测外周血基因组DNA，并确定细胞色素P-450 1A1、谷胱甘肽s转移酶、微粒体环氧化物水解酶和锰超氧化物歧化酶的遗传多态性。我们发现锰超氧化物歧化酶基因多态性、酶靶序列的缬氨酸/丙氨酸多态性与年龄相关性黄斑变性有显著相关性。患者丙氨酸等位基因和丙氨酸/丙氨酸基因型频率增高。我们还观察到微粒体环氧化物水解酶外显子3多态性与年龄相关性黄斑变性的弱关联。细胞色素P-450 1A1、谷胱甘肽s转移酶和染色体体环氧化物水解酶外显子4具有多态性，但其基因型频率分布在患者和对照组之间无统计学差异。提示锰超氧化物歧化酶基因多态性与渗出性老年性黄斑变性有关。微粒体环氧化物水解酶是另一种可能与该病有关的酶。年龄相关性黄斑变性的渗出形式可能具有抗氧化应激和/或外源性药物影响的遗传风险因素。需要进一步研究其他基因与外源代谢酶的关联，以阐明环境-遗传相互作用在年龄相关性黄斑变性的潜在原因。少

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 … More 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