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Ronald Gangnon, Kristine E Lee, Barbara EK Klein, Sudha K Iyengar, Theru A Sivakumaran, Ronald Klein; The Y402H Variant in the Complement Factor H Gene Affects Incidence and Early Progression of Age-Related Macular Degeneration: Results from Multi-state Markov Models Applied to the Beaver Dam Eye Study. Invest. Ophthalmol. Vis. Sci. 2011;52(14):108.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the impact of age, sex and the Y402H variant in the complement factor H (CFH) gene on incidence, progression and regression of age-related macular degeneration (AMD).
Analyses included 3,015 persons, 43 to 86 years of age at the time of initial examination. AMD status on a six-step severity scale was graded from retinal photographs taken at up to 5 study visits between 1988 and 2010. Multi-state Markov models in continuous time were used to model the effects of age, sex and CFH genotype on incidence, progression and regression of AMD and mortality.
Older age was associated with increased incidence of AMD (hazard ratio 2.14 per 10 years, 95% confidence interval [CI] 1.88-2.42), progression of AMD (Level 2 to 3: 1.71, 1.46-2.00; Level 3 to 4: 1.47, 1.19-1.81; Level 4 to geographic atrophy (GA): 1.78, 1.15-2.77; Level 4 to exudative AMD: 1.42, 1.04-1.94) and mortality (3.08, 2.90-3.27), but not with regression of AMD. Male sex was associated with mortality (1.50, 1.35-1.68), but not with incidence, progression or regression of AMD.CFH genotype CC was associated with increased incidence of AMD (1.94, 1.38-2.73), early progression of AMD (Level 2 to 3: 2.32, 1.49-2.61) and mortality (1.43, 1.22-1.67), but not with later progression or regression of AMD relative to the TT genotype. Starting with individuals free of AMD at age 44 years, estimated lifetime incidence of early (level 2) and late (GA or exudative) AMD for those with the CC risk genotype was higher in males [43.7% (95% CI 34.9-52.2); 9.2% (5.3-14.0)] and females [52.5% (42.9-61.5); 16.6% (10.5-23.1)] than for those with the TT genotype [males: 40.6% (34.7-47.1); 3.2% (1.6-5.1)]; females: 40.6% (34.7-47.1); 6.0% (3.5-9.1)].
Using multi-state Markov models, we show that the Y402H risk variant elevates lifetime incidence of both early and late AMD even though it only directly affects incidence and early progression of AMD.
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