Journal article
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
Annals of Medicine, Vol.38(8), pp.592-604
01/01/2006
DOI: 10.1080/07853890601097030
PMID: 17438673
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.
Details
- Title: Subtitle
- 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
- Creators
- Gregory S HagemanLisa S HancoxAndrew J TaiberKaren M GehrsDon H AndersonLincoln V JohnsonMonte J RadekeDavid KavanaghAnna RichardsJohn AtkinsonSeppo MeriJulie BergeronJana ZernantJoanna MerriamBert GoldRando AllikmetsMichael DeanAMD Clinical Study Grp
- Resource Type
- Journal article
- Publication Details
- Annals of Medicine, Vol.38(8), pp.592-604
- Publisher
- Taylor & Francis
- DOI
- 10.1080/07853890601097030
- PMID
- 17438673
- ISSN
- 0785-3890
- eISSN
- 1365-2060
- Language
- English
- Date published
- 01/01/2006
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Microbiology and Immunology; Pathology; Orthopedics and Rehabilitation; Industrial and Systems Engineering; Ophthalmology and Visual Sciences
- Record Identifier
- 9983980396302771
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