Complement factor H polymorphisms, renal phenotypes and age-related macular degeneration: The Blue Mountains Eye Study

C. Xing, T. A. Sivakumaran, J. J. Wang, E. Rochtchina, T. Joshi, W. Smith, P. Mitchell, S. K. Iyengar

Research output: Contribution to journalArticle

35 Scopus citations

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 ∼ 0.98 ml min-1 per 1.73 m2 (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.

Original languageEnglish (US)
Pages (from-to)231-239
Number of pages9
JournalGenes and Immunity
Volume9
Issue number3
DOIs
StatePublished - Apr 1 2008

ASJC Scopus subject areas

  • Immunology
  • Genetics
  • Genetics(clinical)

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    Xing, C., Sivakumaran, T. A., Wang, J. J., Rochtchina, E., Joshi, T., Smith, W., Mitchell, P., & Iyengar, S. K. (2008). Complement factor H polymorphisms, renal phenotypes and age-related macular degeneration: The Blue Mountains Eye Study. Genes and Immunity, 9(3), 231-239. https://doi.org/10.1038/gene.2008.10