Keilhauer, Claudia N. and Fritsche, Lars G. and Guthoff, Rainer and Haubitz, Imme and Weber, Bernhard H. (2013) Age-related macular degeneration and coronary heart disease: Evaluation of genetic and environmental associations. EUROPEAN JOURNAL OF MEDICAL GENETICS, 56 (2). pp. 72-79. ISSN 1769-7212,
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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 Delta CFHR3/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. (C) 2012 Elsevier Masson SAS. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | COMPLEMENT FACTOR-H; INCIDENT MYOCARDIAL-INFARCTION; CARDIOVASCULAR RISK-FACTORS; ATHEROSCLEROTIC LESIONS; EYE DISEASE; FACTOR-B; POLYMORPHISM; MORTALITY; INFLAMMATION; POPULATION; Age-related macular degeneration; Coronary heart disease; Genetic risk factors; Case-control study; CFH Y402H; CFH I62V; Delta CFHR3/CFHR1; ARMS2 A69S |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Humangenetik |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 28 Apr 2020 09:11 |
| Last Modified: | 28 Apr 2020 09:11 |
| URI: | https://pred.uni-regensburg.de/id/eprint/17222 |
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