Coding and noncoding variants in the CFH gene and cigarette smoking influence the risk of age-related macular degeneration in a Japanese population
Coding and noncoding variants in the CFH gene and cigarette smoking influence the risk of age-related macular degeneration in a Japanese population
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DOI：
10.1167/iovs.07-0426
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发表时间：
2007-11-01
影响因子：
4.4
通讯作者：
Yoneya, Shin
中科院分区：
文献类型：
--
作者：
Mori, Keisuke;Gehlbach, Peter L.;Yoneya, Shin
目的.据报道，年龄相关性黄斑变性（AMD）相关的补体因子H（CFH）Y 402 H多态性存在种族差异。这种差异在日本人群中很明显。最近，在高加索人患者中发现了CFH基因中的一种新的单核苷酸多态性（SNP; rs 1410996）与AMD之间的强相关性。本研究旨在调查CFH基因的4种编码和非编码变异体（包括rs 1410996）是否与日本本地无关的AMD患者相关。共招募了188名AMD患者和139名未患AMD的对照受试者进行研究。采用基因分型法检测CFH基因rs 800292、rs 1061170、rs 1410996和rs 2274700 4个SNP位点。通过标准化量表记录每例受试者的全身状况和生活方式（包括吸烟）信息。内含子SNP（rs 1410996）和同义SNP（rs 2274700）与AMD的显著风险相关（分别为P = 2.37 × 10 - 5和3.52 × 10 - 5）。编码变异（rs 800292，I62 V）与AMD之间也有显著相关性（P = 8.63 × 10（-6））。相比之下，Y 402 H变异与AMD无显著相关性（P = 0.101）。两种常见的单倍型与AMD也有显著相关性（P = 1.08 × 10（-3）和2.00 × 10（-5））。在环境因素中，单纯吸烟与老年性黄斑变性有显著相关性（P = 1.17 × 10（-4））。虽然Y 402 H变异与AMD无显著相关性，但CFH基因中的其他编码和非编码变异（包括rs 1410996）和吸烟对日本人群中AMD的风险有中度影响。
PURPOSE. Ethnic variation has been reported in age- related macular degeneration ( AMD) - associated Y402H polymorphism in complement factor H ( CFH). This variation is evident in the Japanese population. Recently a strong association between a novel single- nucleotide polymorphism ( SNP; rs1410996) in the CFH gene and AMD has been identified in Caucasian patients. The present study was undertaken to investigate whether four coding and noncoding variants of the CFH gene, including rs1410996, are associated with AMD in native, unrelated Japanese patients.METHODS. A total of 188 patients with AMD and 139 control subjects without AMD were recruited for the study. Four SNPs ( rs800292, rs1061170, rs1410996, and rs2274700) in the CFH gene were assessed by genotyping assay. The information regarding systemic conditions and lifestyle including smoking were documented in each subject by standardized questionnaire.RESULTS. The intronic SNP ( rs1410996) and the synonymous SNP ( rs2274700) were associated with a significant risk of AMD ( P = 2.37 X 10(-5) and 3.52 X 10(-5), respectively). A significant association was also noted between a coding variant ( rs800292, I62V) and AMD ( P = 8.63 X 10(-6)). In contrast, the Y402H variant showed no significant association with AMD ( P = 0.101). Two common haplotypes also demonstrated significant association with AMD ( P = 1.08 X 10(-3) and 2.00 X 10(-5)). Among the environmental factors, smoking alone had a significant association with AMD ( P = 1.17 X 10(-4)).CONCLUSIONS. Although the Y402H variant was not significantly associated with AMD, other coding and noncoding variants in the CFH gene including rs1410996 and smoking moderately influenced the risk of AMD in a Japanese population.