title: Analysis of candidate genes for age-related macular degeneration subtypes in the Japanese population.
abstract: OBJECTIVE
  Age-related macular degeneration (AMD) is thought to be a polygenetic disease. It is divided into three subtypes; neovascular AMD (nAMD), polypoidal choroidal vasculopathy, and retinal angiomatous proliferation (RAP). These subtypes are thought to have different pathophysiological and genetic backgrounds. We aimed to investigate the relationships between single nucleotide polymorphisms (SNPs) in candidate genes and subtypes of AMD in the Japanese population.
  
  
  METHODS
  We genotyped 685 AMD patients and 277 controls for four SNPs of the selected candidate genes: rs800292 in complement factor H, rs10490924 in age-related maculopathy susceptibility 2 (ARMS2), rs2301995 in elastin (ELN), and rs1801133 in methylenetetrahydrofolate reductase (MTHFR). Case-control studies were performed using these AMD subtypes. Logistic regression analysis was performed using a history of hypertension, diabetes mellitus, and smoking as cardiovascular risks.
  
  
  RESULTS
  The genotype-dominant or recessive distribution of all four SNPs differed significantly between the controls and the AMD patients. In the subtype analysis, there were significant differences between the controls and the AMD patients in genotype distributions. This was true for all AMD subtype analyses of both rs800292 (complement factor H) and rs10490924 (ARMS2). Logistic regression analysis indicated the TT genotype of the ARMS2 gene to be significantly more common in RAP patients (p=1.54×10(-13), odds ratio: 22.18). In contrast, there were significant differences in the genotype distribution between the controls and nAMD patients only for rs2301995 (ELN, p=0.022) and rs1801133 (MTHFR, p=2.50×10(-3)).
  
  
  CONCLUSIONS
  Our results indicate that SNPs of the ARMS2 gene may serve as strong genetic markers of RAP, and that SNPs of the ELN and MTHFR genes are potential genetic markers for nAMD.
authors: Department of Ophthalmology, Nihon University School of Medicine, Tokyo, Japan.
authors: Koji
authors: K
authors: Tanaka
authors: Tomohiro
authors: T
authors: Nakayama
authors: Mitsuko
authors: M
authors: Yuzawa
authors: Zhaoxia
authors: Z
authors: Wang
authors: Akiyuki
authors: A
authors: Kawamura
authors: Ryusaburou
authors: R
authors: Mori
authors: Hiroyuki
authors: H
authors: Nakashizuka
authors: Naoyuki
authors: N
authors: Sato
authors: Yoshihiro
authors: Y
authors: Mizutani
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D017242:Complement Factor H / Q000235:genetics*; D004549:Elastin / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008268:Macular Degeneration / Q000145:classification / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*; D012307:Risk Factors
chemical_list: C514392:ARMS2 protein, human; D005819:Genetic Markers; D011506:Proteins; D017242:Complement Factor H; D004549:Elastin; D042965:Methylenetetrahydrofolate Reductase (NADPH2)