title: Analysis of Genetic and Environmental Risk Factors and Their Interactions in Korean Patients with Age-Related Macular Degeneration.
abstract: OBJECTIVE
  To investigate the association of genetic and environmental factors, and their interactions in Korean patients with exudative age-related macular degeneration (AMD).
  
  
  METHODS
  A total of 314 robustly characterized exudative AMD patients, including 111 PCV (polypoidal choroidal vasculopathy) and 154 typical choroidal neovascularization (CNV), and 395 control subjects without any evidence of AMD were enrolled. Full ophthalmologic examinations including fluorescein angiography (FA), indocyanine green angiography (ICG) and optical coherence tomography (OCT) were done, according to which patients were divided into either PCV or typical CNV. Standardized questionnaires were used to collect information regarding underlying systemic diseases, dietary habits, smoking history and body mass index (BMI). A total of 86 SNPs from 31 candidate genes were analyzed. Genotype association and logistic regression analyses were done and stepwise regression models to best predict disease for each AMD subtype were constructed.
  
  
  RESULTS
  Age, spherical equivalent, myopia, and ever smoking were associated with exudative AMD. Age, hypertension, hyperlipidemia, spherical equivalent, and myopia were risk factors for typical CNV, while increased education and ever smoking were significantly associated with PCV (p<.05 for all). Four SNPs, ARMS2/HTRA1 rs10490924, rs11200638, and rs2736911, and CFH rs800292, showed association with exudative AMD. Two of these SNPs, ARMS2/HTRA1 rs10490924 and rs11200638, showed significant association with typical CNV and PCV specifically. There were no significant interactions between environmental and genetic factors. The most predictive disease model for exudative AMD included age, spherical equivalent, smoking, CFH rs800292, and ARMS2 rs10490924 while that for typical CNV included age, hyperlipidemia, spherical equivalent, and ARMS2 rs10490924. Smoking, spherical equivalent, and ARMS2 rs10490924 were the most predictive variables for PCV. When comparing PCV cases to CNV cases, age, BMI, and education were the most predictive risk factors of PCV.
  
  
  CONCLUSIONS
  Only one locus, the ARMS2/HTRA1 was a significant genetic risk factor for Korean exudative AMD, including its subtypes, PCV and typical CNV. Stepwise regression revealed that CFH was important to risk of exudative AMD in general but not to any specific subtype. While increased education was a unique risk factor to PCV when compared to CNV, this association was independent of refractive error in this homogenous population from South Korea. No significant interactions between environmental and genetic risk factors were observed.
authors.affiliation: Department of Ophthalmology, Seoul National University College of Medicine, Seoul, Korea; Department of Ophthalmology, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Se Joon
authors.initials: SJ
authors.lastname: Woo
authors.affiliation: Department of Ophthalmology, Seoul National University College of Medicine, Seoul, Korea; Department of Ophthalmology, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea.
authors.forename: Jeeyun
authors.initials: J
authors.lastname: Ahn
authors.affiliation: Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, United States of America.
authors.forename: Margaux A
authors.initials: MA
authors.lastname: Morrison
authors.affiliation: Medical Research Collaborating Center, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: So Yeon
authors.initials: SY
authors.lastname: Ahn
authors.affiliation: Medical Research Collaborating Center, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Jaebong
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Psychiatry, Seoul National University College of Medicine, Seoul, Korea; Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Ki Woong
authors.initials: KW
authors.lastname: Kim
authors.affiliation: Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, United States of America.
authors.forename: Margaret M
authors.initials: MM
authors.lastname: DeAngelis
authors.affiliation: Department of Ophthalmology, Seoul National University College of Medicine, Seoul, Korea; Department of Ophthalmology, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Kyu Hyung
authors.initials: KH
authors.lastname: Park
mesh_terms: D000368:Aged; D044466:Asian People / Q000235:genetics*; D020256:Choroidal Neovascularization / Q000150:complications; D004777:Environment; D005260:Female; D059647:Gene-Environment Interaction; D006801:Humans; D008268:Macular Degeneration / Q000150:complications / Q000453:epidemiology* / Q000235:genetics*; D008297:Male; D056910:Republic of Korea / Q000453:epidemiology; D012307:Risk Factors