title: Combined effects of complement factor H genotypes, fish consumption, and inflammatory markers on long-term risk for age-related macular degeneration in a cohort.
abstract: At baseline in 1992-1994, the authors assessed the combined effects of complement factor H (CFH) genotypes with smoking, fish consumption, and inflammatory markers on the risk of age-related macular degeneration (AMD) in 3,654 persons aged > or =49 years. They reexamined 75% of the survivors after 5 and 10 years, confirming incident AMD by side-by-side photographic grading. Of the 2,452 persons followed in the Blue Mountains Eye Study, 1,881 were genotyped (rs1061170), with CC, CT, and TT identified in 13.6%, 46.7%, and 39.7%, respectively. AMD risk increased with each additional C allele (early AMD: age- and sex-adjusted relative risk (RR) = 1.6, 95% confidence interval (CI): 1.2, 1.9; late AMD: RR = 2.3, 95% CI: 1.5, 3.6). Late AMD risk among current smokers with the CC/CT genotypes (RR = 10.7, 95% CI: 3.4, 33.9) was 5-fold that for genotypically similar nonsmokers (RR = 2.2, 95% CI: 0.9, 5.5) versus current nonsmokers with TT genotypes. Weekly compared with less than weekly consumption of fish was associated with reduced late AMD risk in participants with the CC genotype (RR = 0.15, 95% CI: 0.03, 0.8) but not the CT (RR = 0.7, 95% CI: 0.3, 2.0) or TT (RR = 1.3, 95% CI: 0.2, 7.2) genotypes. This study documents joint contributions from genetic and systemic factors in determining the progression of AMD.
authors.affiliation: Vision Research, Department of Ophthalmology and the Westmead Millennium Institute, University of Sydney, Sydney, New South Wales, Australia. jiejin_wang@wmi.usyd.edu.au
authors.forename: Jie Jin
authors.initials: JJ
authors.lastname: Wang
authors.forename: Elena
authors.initials: E
authors.lastname: Rochtchina
authors.forename: Wayne
authors.initials: W
authors.lastname: Smith
authors.forename: Ronald
authors.initials: R
authors.lastname: Klein
authors.forename: Barbara E K
authors.initials: BE
authors.lastname: Klein
authors.forename: Tripti
authors.initials: T
authors.lastname: Joshi
authors.forename: Theru A
authors.initials: TA
authors.lastname: Sivakumaran
authors.forename: Sudha
authors.initials: S
authors.lastname: Iyengar
authors.forename: Paul
authors.initials: P
authors.lastname: Mitchell
mesh_terms: D000368:Aged; D015331:Cohort Studies; D017242:Complement Factor H / Q000235:genetics*; D004032:Diet; D015987:Effect Modifier, Epidemiologic; D005260:Female; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008268:Macular Degeneration / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009517:New South Wales / Q000453:epidemiology; D012307:Risk Factors; D017747:Seafood; D012907:Smoking / Q000009:adverse effects* / Q000453:epidemiology; D011795:Surveys and Questionnaires
chemical_list: D017242:Complement Factor H