한국인 나이관련황반변성에서 유전학적 요인과 환경 요인의 관련성 분석 ; Association analysis of genetic and environmental factors in Korean patients with age-related macular degeneration

Purpose: This study was aimed to investigate the associations of genetic factors, environmental factors, and their interactions with Age-related Macular Degeneration (AMD) in Korean patients and normal elderly people using candidate gene single nucleotide polymorphism (SNP) analysis. Methods: This was a case-control study including 463 Korean AMD patients and 395 normal Korean control subjects. 86 SNPs from 31 candidate genes were analyzed using multiplex PCR (iPLEX, Sequenom, San Diego, CA). Demographic and environmental factors were age, sex, smoking, body mass index, systemic diseases and diet. Interaction of SNP genotypes with environmental factors were also analyzed in association with risk of AMD. Detailed analyses were performed regarding the subtypes of AMD including polypoidal choroidal vasculopathy (PCV). Results: Variants in two genetic loci in 10q26 (rs10490924, ARMS2, OR=2.86, log additive P=3.18E-21 and rs11200638, HTRA1, OR=2.79, log additive P=2.69E-21) showed significant associations with AMD. Variants in rs800292 (CFH) was significantly associated with only exudative AMD (OR=1.672, 95%CI=1.317-2.122, P=2.41E-5). Among SNPs in CFH, rs800292 showed the strongest association with AMD (log additive P=0.000709) and rs1061170 (Y402H) variant was not associated with AMD (log additive P=0.01518). No reported SNPs in other genes including C2, CFB, CFI, SERPING1, APOE, CRP, VEGF, TLR3 and ELN showed associations with AMD (P>0.05). While variants in ARMS2/HTRA1 were associated with both early and late AMD, CFH variants was associated with only late AMD. The population-attributable risk was 65.9% for rs10490924 (ARMS2), 65.1% for HTRA1 (rs11200638), and 40.5% for rs800292 (CFH). The association of AMD with SNPs in ARMS2/HTRA1 and CFH were amplified when interacted with smoking and the interaction was more distinct with PCV than other subtypes of AMD. The Joint effect of ARMS2/HTRA1 and smoking for PCV was greater than a mere additive scale (Synergy index=2.470 and 2.517). Among dietary factors, the ...