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

Genes & Immunity volume 9, pages 231–239 (2008)Cite this article

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.

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Acknowledgements

We thank the two anonymous reviewers for their insightful comments that led to great improvements in this article. This study was supported, in part, by US Public Health Service research grants GM28356, from the National Institute of General Medical Sciences, grant EY015810 from the National Eye Institute, and grants 974159 and 211069 from NHMRC.

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Authors and Affiliations

  1. Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, USA

    C Xing, T A Sivakumaran, T Joshi & S K Iyengar

  2. Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX, USA

    C Xing

  3. McDermott Center of Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX, USA

    C Xing

  4. Department of Ophthalmology Westmead Millennium Institutes, Centre for Vision Research, University of Sydney, Sydney, Australia

    J J Wang, E Rochtchina & P Mitchell

  5. Centre for Clinical Epidemiology and Biostatistics, University of Newcastle, Newcastle, Australia

    W Smith

  6. Department of Genetics, Case Western Reserve University, Cleveland, OH, USA

    S K Iyengar

  7. Department of Ophthalmology, Case Western Reserve University, Cleveland, OH, USA

    S K Iyengar

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Xing, C., Sivakumaran, T., Wang, J. et al. Complement factor H polymorphisms, renal phenotypes and age-related macular degeneration: the Blue Mountains Eye Study. Genes Immun 9, 231–239 (2008). https://doi.org/10.1038/gene.2008.10

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