Effect of the Y402H Variant in the Complement Factor H Gene on the Incidence and Progression of Age-Related Macular Degeneration Results From Multistate Models Applied to the Beaver Dam Eye Study
Effect of the Y402H Variant in the Complement Factor H Gene on the Incidence and Progression of Age-Related Macular Degeneration Results From Multistate Models Applied to the Beaver Dam Eye Study
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DOI：
10.1001/archophthalmol.2012.693
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发表时间：
2012-09-01
影响因子：
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通讯作者：
Klein, Ronald
中科院分区：
文献类型：
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作者：
Gangnon, Ronald E.;Lee, Kristine E.;Klein, Ronald
目的：采用多状态模型研究年龄、性别和补体因子H(CFH)基因Y402H变异对老年性黄斑变性(AMD)发病、进展和消退的影响，以及这些因素和AMD对死亡率的影响。AMD的状况是根据1988年至2010年间多达5次研究访问时拍摄的视网膜照片进行5级严重程度分级的。结果：相对于TT基因型，CFH Y402H基因型与AMD发病率增加(无至轻度早期AMD，1.98；1.57~2.49)，AMD进展(轻度早期AMD，1.73；1.29~2.33；中重度早期AMD，1.30；0.86~1.94；重度早至晚期AMD，1.72；1.01~2.91)，但与AMD的消退或死亡率无关。晚期AMD患者的死亡率(1.37；1.15-1.62)高于非AMD患者，但早期AMD患者的死亡率无显著差异。结论：运用多状态模型，我们发现Y402H风险变量与早期AMD的终生发病率和早期到晚期AMD的进展相关，而晚期AMD与死亡风险相关。
Objectives: To investigate the effect of age, sex, and the Y402H variant in the complement factor H (CFH) gene on the incidence, progression, and regression of age-related macular degeneration (AMD) as well as the effect of these factors and AMD on mortality, using multistate models.Methods: Analyses included 4379 persons aged 43 to 84 years at the time of the census. The status of AMD on a 5-level severity scale was graded from retinal photographs taken at up to 5 study visits between 1988 and 2010. Multistate models in continuous time were used to model the effects of age, sex, and CFH genotype on the incidence, progression, and regression of AMD and mortality.Results: The CFH Y402H genotype CC was associated, relative to genotype TT (reported as hazard ratio; 95% CI), with increased incidence of AMD (no to minimally severe early AMD, 1.98; 1.57-2.49), progression of AMD (minimally severe early to moderately severe early AMD, 1.73; 1.29-2.33; moderately severe early to severe early AMD, 1.30; 0.86-1.94; and severe early to late AMD, 1.72; 1.01-2.91) but not with regression of AMD or mortality. Late AMD was associated with increased mortality (1.37; 1.15-1.62) relative to no AMD, but earlier stages of AMD were not.Conclusions: Using the multistate models, we show that the Y402H risk variant is associated with lifetime incidence of early AMD and progression of early to late AMD and that late AMD is associated with mortality risk.