补体因子H与ARMS2基因多态性与年龄相关性黄斑变性的关联研究

方凯， 田君， 秦雪英等、基因多态性与年龄相关性黄斑变性的关联研究、[J].中华疾病控制杂志,2012,16(6):467-471

黄斑变性; 补体因子H; 疾病遗传易感性

方凯1， 田君1， 秦雪英1， 陈卿1， 李娟1， 于文贞2， 侯婧2， 陈大方1， 胡永华1， 黎

1北京大学公共卫生学院流行病与卫生统计学系， 北京　100191　2北京大学人民医院眼科， 北京　1

2012

467-471

知网,万方

目的　探讨补体因子H(complement factor H，CFH)基因Y402H和年龄相关性黄斑变性易感基因2(age-related maculopathy susceptibility 2，ARMS2)A69S多态性与年龄相关性黄斑变性(age-related macular degeneration， AMD)的关联，并分析Y402H和A69S与环境因素之间的交互作用。方法　采用以医院为基础的多中心病例对照研究，共纳入病例545人，对照480人，使用统一的调查问卷收集人口学资料和环境因素，并进行体格检查和眼科检查，纳入成功鉴定基因型的病例535人，对照469人，应用Logistic回归进行多因素分析，并计算交互作用超额危险度(relative excess risk of interaction，RERI)、交互作用归因比(attributable proportion of interaction，API)及交互作用指数S(interaction index S，Index S)。结果　Y402H和A69S均与AMD有相关性，在对可能的混杂因素进行调整后，吸烟与Y402H的RERI、API及Index S分别为0.919、28.210%、2.433，吸烟与A69S的RERI、API和Index S分别为0.869、24.438%、2.108。结论　CFH Y402H和ARMS2 A69S基因多态性均与AMD相关，但Y402H突变率低，Y402H和A69S均与吸烟在AMD的发生中存在交互作用。 Objective　To assess the association of complement factor H(CFH) Y402H and age-related maculopathy susceptibility 2(ARMS2) A69S with age-related macular degeneration in a Chinese population， as well as its interaction with environmental risk factors. Methods　A national cross-sectional multicenter hospital-based survey was conducted. A total of 545 age-related macular degeneration(AMD) patients and 480 controls， aged 50 years or older consented to participate in the study. Questionnaire was designed to collect information on demographic characteristics and behavior factors; moreover， physical examination and ophthalmology examination were done for each participant. The genotype was obtained in 535 AMD patients and 469 controls， and available data was analyzed by multivariate methods using Logistic regression， and the gene-environment interaction was analyzed by using an additive effects model. Results　Y402H and A69S were both found to be associated with the risk of AMD. After adjusting some confounding factors， significant positive interaction were observed between smoking， CFH Y402H， and ARMS2 A69S， and the relative excess risk of interaction(RERI)， attributable proportion of interaction(API)， and the interaction index S(Index S) were 0.919 vs 0.869， 28.210% vs 24.438% and 2.433 vs 2.108， respectively. Conclusions　Common polymorphisms in the genes CFH and ARMS2 are independently related to AMD， and smoking modifies the association of CFH Y402H and ARMS2 A69S with AMD.