Purpose:
To investigate genetic and environmental risk factors in Korean age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) and assess the effect of gene-environment interaction on the pathogenesis of the two diseases.
Methods:
A case-control study involving 463 AMD patients and 395 normal controls was done. Demographic data including diet and smoking history were assessed using questionnaires and subjects were genotyped for 4 single nucleotide polymorphisms (SNPs) significantly associated with AMD. To assess the effect of smoking on each of the AMD subtypes, multivariate analysis with smoking history, baseline demographics and genetic data was done.
Results:
On the multivariate analysis adjusted for age, gender, body mass index, and diet, smoking history showed significant association with exudative AMD (OR=1.800, p=0.001). Variants in ARMS2 (rs10490924), HTRA1 (rs11200638), and CFH (rs800292) showed significant association with AMD and PCV. Smoking increased odds ratio (OR) of the homozygote (AA) in HTRA1 rs11200638 from 7.92 (never smoked) to 10.26 (ever smoked) for AMD, and 7.15 (never smoked) to 22.25 (ever smoked) for PCV, showing high correlation with PCV. The synergy index of ARMS2 and HTRA1 with smoking was 2.470 (p=0.018) and 2.517 (p=0.017) for the homozygote variant, respectively, indicating the joint effect of ARMS2/HTRA1 and smoking on PCV was greater than the additive scale.
Conclusions:
Smoking history and genetic risk factors are associated with AMD and PCV in the Korean population. Correlation between genetic and environmental (smoking) risk factors was observed in PCV, implying that gene-environment interaction plays an important role in the pathogenesis of PCV.
Keywords: age-related macular degeneration • genetics • retina