title: Complement factor H polymorphisms, renal phenotypes and age-related macular degeneration: the Blue Mountains Eye Study.
abstract: Complement factor H (CFH) is a key regulator of the alternative pathway of complement and its mutations have been associated with membranoproliferative glomerulonephritis type II, atypical hemolytic uremic syndrome and age-related macular degeneration (AMD), suggesting that alternative pathway dysregulation is a common pathogenetic feature of these ocular and renal conditions. In this study we tested the hypothesis that common CFH variants have a global role in renal function in the Australian population-based Blue Mountains Eye Study (BMES). We replicated the association of I62V with estimated glomerular filtration rate (GFR; P=0.017) and creatinine clearance (CRCL; P=0.015). The minor allele of I62V (G) was deleterious: adding one copy of the G allele decreased GFR/CRCL by approximately 0.98 ml min(-1) per 1.73 m(2) (95% confidence interval (CI): 0.97, 0.99). We also replicated the association of Y402H with AMD and provided an unbiased estimate of population attributable risk (PAR). The minor allele of Y402H (C) was deleterious: the odds ratio estimate of CC genotype compared to TT was 1.87 (95% CI: 1.44, 2.45). The PAR of the C allele was estimated as 0.22 (95% CI: 0.15, 0.28). In summary, in the BMES population we confirmed the association between I62V and renal function, as measured by the estimated GFR, plus the association of Y402H with both early- and late-stage AMD.
authors.affiliation: Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: C
authors.initials: C
authors.lastname: Xing
authors.forename: T A
authors.initials: TA
authors.lastname: Sivakumaran
authors.forename: J J
authors.initials: JJ
authors.lastname: Wang
authors.forename: E
authors.initials: E
authors.lastname: Rochtchina
authors.forename: T
authors.initials: T
authors.lastname: Joshi
authors.forename: W
authors.initials: W
authors.lastname: Smith
authors.forename: P
authors.initials: P
authors.lastname: Mitchell
authors.forename: S K
authors.initials: SK
authors.lastname: Iyengar
mesh_terms: D017242:Complement Factor H / Q000235:genetics; D003170:Complement Pathway, Alternative / Q000235:genetics*; D005787:Gene Frequency; D005828:Genetics, Population; D006801:Humans; D007668:Kidney / Q000473:pathology*; D008268:Macular Degeneration / Q000453:epidemiology* / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics; D009517:New South Wales / Q000453:epidemiology; D016017:Odds Ratio; D010641:Phenotype
chemical_list: C493495:CFH protein, human; D017242:Complement Factor H