No Association of the Angiotensin–converting Enzyme (ACE) Gene Insertion/Deletion Polymorphism With Age–related Macular Degeneration

Abstract

Abstract: : Purpose: Age–related macular degeneration (AMD) is the commonest cause of irreversible blindness affecting the elderly population in the western world. There is good evidence that genetic factors influence susceptibility to AMD. An association has been reported between an Alu element insertion/ deletion polymorphism in the angiotensin I – converting enzyme (ACE) gene and susceptibility to AMD, the presence of the Alu insertion being protective against the atrophic form of the disease. The current study was conducted in order to further investigate the association between the Alu insertion/ deletion polymorphism and advanced AMD (defined as the presence of either choroidal neovascularisation CNV or geographic atrophy GA). Methods: 364 unrelated Caucasian patients with advanced AMD (216 pure CNV, 89 pure GA, 59 mixed CNV and GA) were compared with 261 control subjects. All patients completed a detailed questionnaire of medical, social and family history. Ocular examination was performed by an ophthalmologist and stereoscopic colour fundus photographs were obtained by a certified photographer and formally graded. All patients donated a blood sample for genetic studies. The polymerase chain reaction (PCR) was used on genomic DNA to determine ACE genotype. Results: Univariate analysis showed no significant difference for insertion (I) and deletion (D) allele frequencies (Χ2=0.7 d.f.=1, p=0.41). The distribution of the ACE genotypes I/I, I/D and D/D in cases (79 [22%], 201 [55%], 84 [23%]) was not significantly different from controls (56 [21%], 133 [51%], 72 [28%]). A logistic regression model (adjusting for the significant effects of age, family history of AMD and smoking) revealed no evidence of a significant association between the presence of AMD and I/D (OR=0.98, 95% CI 0.62–1.54) or D/D (OR=0.77, 95% CI 0.46–1.28) in comparison to the I/I genotype. Subgroup analysis of different AMD phenotypes including GA showed no evidence of association. Conclusions: We have investigated a large series of cases and controls and found no evidence that the ACE gene insertion/ deletion polymorphism influences susceptibility to AMD. Further work on other ACE gene polymorphisms is underway in order to further evaluate the possible role of the ACE gene in AMD.

Keywords: age-related macular degeneration • genetics • candidate gene analysis