Age-related macular degeneration and coronary heart disease: evaluation of genetic and environmental associations

An association between coronary heart disease (CHD) and age-related macular degeneration (AMD) has long been postulated but results from epidemiological case-control studies, and genetic analyses have been ambiguous. In this study we illuminate the association between AMD and CHD with respect to genetic and environmental risk factors, age of disease onset and AMD subgroups. AMD patients (n = 1036) and age-matched control subjects (n = 412) between 68 and 95 years of age were included in the case-control study. A medical history of CHD, cerebral stroke and arterial hypertension was determined for each individual. The assessment of interacting factors included the current use of systemic medications and smoking habits. Analysis of AMD associated genetic variants included frequent polymorphisms at the complement factor H (CFH, MIM 134370) gene (rs1061170 [p.Y402H], rs800292 [p.I62V]), the complement factor H-related 3 (CFHR3, MIM 605336)/complement factor H-related 1 (CFHR1, MIM 134371) locus (rs6677604; proxy for ΔCFHR3/CFHR1; r(2) = 0.97) as well as the age-related maculopathy susceptibility 2 (ARMS2, MIM 611313) gene (rs10490924 [p.A69S]). Logistic regression identified a significant positive association of AMD with AMD-risk variants in CFH, ARMS2, and smoking ≥ 20 packs/year. A history of CHD and the current use of antihyperuricemic agents were inversely associated with the disease. Significantly fewer patients with rs6677604 nonrisk genotype A/A regularly used statins. ARMS2:p.A69S risk variant was significantly associated with exsudative AMD. AMD patients with risk variants at rs1061170 (CFH:p.Y402H) and ARMS2 and smokers (≥20 packs/year) were significantly earlier affected by AMD than those carrying the non-risk variants at each locus. Our data support three major conclusions. First, the age of AMD onset is significantly influenced by genetic and environmental risk factors. Second, in support of previous reports we also show that the ARMS2 rs10490924:T allele is significantly linked to exsudative AMD. And finally, a self-reported history of CHD was inversely associated with AMD in this study. Novel therapeutic strategies aiming at preventing the development of AMD may considerably differ from those that have been developed to treat cardiovascular disorders as both common disorders likely underlie different pathomechanisms.