title: Lens status influences the association between CFH polymorphisms and age-related macular degeneration: findings from two population-based studies in Singapore.
abstract: OBJECTIVE
  To determine the differential effects of genetic polymorphism in CFH and ARMS2 on risk of age-related macular degeneration (AMD) between phakic vs. pseudophakic/aphakic eyes.
  
  
  METHODS
  9,529 eyes of 4,918 participants from the Singapore Malay Eye Study and Singapore Indian Eye Study were analyzed. Participants had detailed eye examinations, including slit-lamp examinations and dilated fundus photography. AMD grading was performed according to the Wisconsin age-related maculopathy grading system. Lens status was defined. Single nucleotide polymorphisms (SNPs) rs10801555 (Y402H) within CFH and rs3750847 in ARMS2 were assessed. The main outcome measure was early AMD or any AMD.
  
  
  RESULTS
  No significant associations between the CFH Y402H genotypes and early AMD were found in phakic individuals. In contrast, among pseudophakic/aphakic individuals, the CFH Y402H risk genotypes were significantly associated with higher odds of early AMD, with an OR of 1.57 (95% CI: 1.07-2.29) for GA genotype and 2.40 (95% CI: 1.25-4.61) for AA genotype, compared to those with GG genotype. There was significant interaction between pseudophakic/aphakic status and CFH Y402H variant on risk of early AMD (p = 0.037), adjusting for age, gender, and the first 5 genetic principal components. No significant interaction was found between lens status and ARMS2 rs3750847.
  
  
  CONCLUSIONS
  CFH genetic polymorphism and pseudophakic/aphakic status may have a potential synergistic effect on early AMD, suggesting roles for the complement system and related pathways in the pathogenesis of AMD in eyes after cataract surgery.
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore.
authors.forename: Chee Wai
authors.initials: CW
authors.lastname: Wong
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore; Department of Ophthalmology, National University of Singapore and National University Health System, Singapore, Singapore.
authors.forename: Jiemin
authors.initials: J
authors.lastname: Liao
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore; Duke-NUS Graduate Medical School, Singapore, Singapore.
authors.forename: Gemmy C
authors.initials: GC
authors.lastname: Cheung
authors.affiliation: Division of Human Genetics, Genome Institute of Singapore, Singapore, Singapore.
authors.forename: Chiea Chuen
authors.initials: CC
authors.lastname: Khor
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore; Duke-NUS Graduate Medical School, Singapore, Singapore.
authors.forename: Eranga N
authors.initials: EN
authors.lastname: Vithana
authors.affiliation: Centre for Vision Research, Department of Ophthalmology, Westmead Millennium Institute, University of Sydney, Sydney, Australia.
authors.forename: Jie Jin
authors.initials: JJ
authors.lastname: Wang
authors.affiliation: Centre for Vision Research, Department of Ophthalmology, Westmead Millennium Institute, University of Sydney, Sydney, Australia.
authors.forename: Paul
authors.initials: P
authors.lastname: Mitchell
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore; Department of Ophthalmology, National University of Singapore and National University Health System, Singapore, Singapore.
authors.forename: Tin
authors.initials: T
authors.lastname: Aung
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore; Department of Ophthalmology, National University of Singapore and National University Health System, Singapore, Singapore; Duke-NUS Graduate Medical School, Singapore, Singapore.
authors.forename: Tien Y
authors.initials: TY
authors.lastname: Wong
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore; Department of Ophthalmology, National University of Singapore and National University Health System, Singapore, Singapore; Duke-NUS Graduate Medical School, Singapore, Singapore.
authors.forename: Ching-Yu
authors.initials: CY
authors.lastname: Cheng
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001035:Aphakia / Q000235:genetics; D044466:Asian People / Q000235:genetics; D017242:Complement Factor H / Q000235:genetics*; D005260:Female; D006801:Humans; D007908:Lens, Crystalline; D008268:Macular Degeneration / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D054120:Phakic Intraocular Lenses; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*; D012307:Risk Factors; D012846:Singapore / Q000453:epidemiology
chemical_list: C514392:ARMS2 protein, human; D011506:Proteins; D017242:Complement Factor H