title: ARMS2 increases the risk of early and late age-related macular degeneration in the European Eye Study.
abstract: OBJECTIVE
  To study associations between severity stages of early and late age-related macular degeneration (AMD) and genetic variations in age-related maculopathy susceptibility 2 (ARMS2) and complement factor H (CFH) and to investigate potential interactions between smoking and ARMS2.
  
  
  METHODS
  Population-based, cross-sectional European Eye Study in 7 countries in Europe.
  
  
  METHODS
  Four thousand seven hundred fifty participants, 65 years of age and older, recruited through random sampling.
  
  
  METHODS
  Participants were classified on the basis of the more severely affected eye into 5 mutually exclusive AMD severity stages ranging from no AMD, 3 categories of early AMD, and late AMD. History of cigarette smoking was available and allowed classification into never, former, and current smokers, with the latter 2 groups combined into a single category of ever smokers for analysis. Genotyping was performed for single nucleotide polymorphisms rs10490924 and rs4146894 in ARMS2 and rs1061170 in CFH. Associations were analyzed by logistic regression.
  
  
  METHODS
  Odds ratios (ORs) for stage of AMD associated with genetic variations in ARMS2 and CFH and interactions between ARMS2 and smoking status.
  
  
  RESULTS
  Early AMD was present in 36.4% and late AMD was present in 3.3% of participants. Data on both genotype and AMD were available for 4276 people. The ORs for associations between AMD stage and ARMS2 increased monotonically with more severe stages of early AMD and were altered little by adjustment for potential confounders. Compared with persons with no AMD, carriers of the TT genotype for rs10490924 in ARMS2 had a 10-fold increase in risk of late AMD (P<3 × 10(-20)). The ORs for associations with CFH were similar for stage 3 early AMD and late AMD. Interactions between rs10490924 in ARMS2 and smoking status were significant in both unadjusted and adjusted models (P = 0.001). The highest risk was observed in those doubly homozygous for rs10490924 and rs1061170 in CFH (OR, 62.3; 95% confidence interval, 16-242), with P values for trend ranging from 0.03 (early AMD, stage 1) to 1 × 10(-26) (late AMD).
  
  
  CONCLUSIONS
  A strong association was demonstrated between all stages of AMD and genetic variation in ARMS2, and a significant gene-environment interaction with cigarette smoking was confirmed.
authors.affiliation: Centre for Vision and Vascular Science, The Queen's University of Belfast, Belfast, United Kingdom. u.chakravarthy@qub.ac.uk
authors.forename: Usha
authors.initials: U
authors.lastname: Chakravarthy
authors.forename: Gareth J
authors.initials: GJ
authors.lastname: McKay
authors.forename: Paulus T V M
authors.initials: PT
authors.lastname: de Jong
authors.forename: Mati
authors.initials: M
authors.lastname: Rahu
authors.forename: Johan
authors.initials: J
authors.lastname: Seland
authors.forename: Gisele
authors.initials: G
authors.lastname: Soubrane
authors.forename: Laura
authors.initials: L
authors.lastname: Tomazzoli
authors.forename: Fotis
authors.initials: F
authors.lastname: Topouzis
authors.forename: Johannes R
authors.initials: JR
authors.lastname: Vingerling
authors.forename: Jesus
authors.initials: J
authors.lastname: Vioque
authors.forename: Ian S
authors.initials: IS
authors.lastname: Young
authors.forename: Reecha
authors.initials: R
authors.lastname: Sofat
authors.forename: Aroon D
authors.initials: AD
authors.lastname: Hingorani
authors.forename: Astrid E
authors.initials: AE
authors.lastname: Fletcher
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D017242:Complement Factor H / Q000235:genetics; D003430:Cross-Sectional Studies; D005060:Europe; D005260:Female; D059647:Gene-Environment Interaction; D060005:Genotyping Techniques; D006801:Humans; D008268:Macular Degeneration / Q000145:classification / Q000235:genetics*; D008297:Male; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011506:Proteins / Q000235:genetics*; D012307:Risk Factors; D012907:Smoking / Q000235:genetics; D011795:Surveys and Questionnaires
chemical_list: C514392:ARMS2 protein, human; C493495:CFH protein, human; D011506:Proteins; D017242:Complement Factor H