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Extended haplotypes in the complement factor H (CFH) and CFH-related (CFHR) family of genes protect against age-related macular degeneration: Characterization, ethnic distribution and evolutionary implications

  1. Author:
    Hageman, G. S.
    Hancox, L. S.
    Taiber, A. J.
    Gehrs, K. M.
    Anderson, D. H.
    Johnson, L. V.
    Radeke, M. J.
    Kavanagh, D.
    Richards, A.
    Atkinson, J.
    Meri, S.
    Bergeron, J.
    Zernant, J.
    Merriam, J.
    Gold, B.
    Allikmets, R.
    Dean, Michael
    Grp, A. M. D. C. S.

  2. Author Address

    Univ Iowa, Dept Ophthalmol & Visual Sci, Cell Biol & Funct Genom Lab, Iowa City, IA 52240 USA. NCI, Lab Genom Divers, Frederick, MD 21701 USA. NCI, SAIC Frederick, Frederick, MD 21701 USA. Univ Calif Santa Barbara, Neurosci Res Inst, Santa Barbara, CA 93106 USA. Washington Univ, Sch Med, Dept Med, Div Rheumatol, St Louis, MO 63130 USA. Univ Helsinki, Haartman Inst, Dept Bacteriol & Immunol, FIN-00014 Helsinki, Finland. Columbia Univ, Dept Ophthalmol, New York, NY 10027 USA. Columbia Univ, Dept Pathol & Cell Biol, New York, NY 10027 USA.;Hageman, GS, Univ Iowa, Dept Ophthalmol & Visual Sci, Cell Biol & Funct Genom Lab, 11190E PFP,200 Hawkins Dr, Iowa City, IA 52240 USA.;dean@ncifcrf.gov
    1. Year: 2006
  2. Journal: Annals of Medicine
    1. 38
    2. 8
    3. Pages: 592-604
  4. Type of Article: Article
  5. ISSN: 0785-3890
  1. Abstract:

    Background. Variants in the complement factor H gene (CFH) are associated with age-related macular degeneration (AMD). CFH and five CFH-related genes (CFHR1-5) lie within the regulators of complement activation (RCA) locus on chromosome 1q32. Aims and Methods. In this study, the structural and evolutionary relationships between these genes and AMD was refined using a combined genetic, molecular and immunohistochemical approach. Results. We identify and characterize a large, common deletion that encompasses both the CFHR1 and CFHR3 genes. CFHR1, an abundant serum protein, is absent in subjects homozygous for the deletion. Genotyping analyses of AMD cases and controls from two cohorts demonstrates that deletion homozygotes comprise 1.1% of cases and 5.7% of the controls (chi-square = 32.8; P = 1.6 E-09). CFHR1 and CFHR3 transcripts are abundant in liver, but undetectable in the ocular retinal pigmented epithelium/choroid complex. AMD-associated CFH/CFHR1/CFHR3 haplotypes are widespread in human populations. Conclusion. The absence of CFHR1 and/or CFHR3 may account for the protective effects conferred by some CFH haplotypes. Moreover, the high frequencies of the 402H allele and the delCFHR1/CFHR3 alleles in African populations suggest an ancient origin for these alleles. The considerable diversity accumulated at this locus may be due to selection, which is consistent with an important role for the CFHR genes in innate immunity.

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  2. DOI: 10.1080/07853890601097030
  3. PMID: 28950782
  4. View record in Web of Science®
  5. WOS: 000243431600006

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