A common CFH haplotype, with deletion of CFHR1 and CFHR3, is associated with lower risk of age-related macular degeneration

  title={A common CFH haplotype, with deletion of CFHR1 and CFHR3, is associated with lower risk of age-related macular degeneration},
  author={Anne E. Hughes and Nick Orr and Hossein Esfandiary and Martha L Diaz-Torres and Timothy H. J. Goodship and Usha Chakravarthy},
  journal={Nature Genetics},
Age-related macular degeneration (AMD; OMIM #603075) is the most frequent cause of visual impairment in the elderly population, with severe disease affecting nearly 10% of individuals of European descent over the age of 75 years. It is a complex disease in which genetic and environmental factors contribute to susceptibility. Complement factor H (CFH) has recently been identified as a major AMD susceptibility gene, and the Y402H polymorphism has been proposed as the likely causative factor. We… Expand
Deletion of CFHR3 and CFHR1 genes in age-related macular degeneration.
Deletion of CFHR1 and CFHR3 may account for a small portion of the protection from AMD associated with particular haplotypes in CFH, which suggests that other protective variants in this region have yet to be discovered. Expand
Deletion of CFHR 3 and CFHR 1 genes in age-related macular degeneration
Age-related macular degeneration (AMD) impairs vision for 7.5 million Americans. Both susceptibility variants and protective haplotypes in the complement factor H (CFH) gene modulate risk for AMD.Expand
Common haplotypes at the CFH locus and low-frequency variants in CFHR2 and CFHR5 associate with systemic FHR concentrations and age-related macular degeneration
FHR proteins are identified as key proteins in the AMD disease mechanism and therapies that modulate FHR proteins might be effective for treating or preventing progression of AMD. Expand
Relevance of complement factor H-related 1 (CFHR1) genotypes in age-related macular degeneration.
A relevant role of CFHR1 in the pathogenesis of AMD is supported and a peculiar genotype-phenotype correlation between theCFHR1 alleles and different diseases is illustrated, which may have important implications for understanding the pathophysiology of AMD. Expand
Influence of CFH, HTRA1 and ARMS2 haplotype polymorphisms in the development of age-related macular disease.
Haplotypes which combine "risk genotypes", demonstrated in previous studies, of the authors' analyzed polymorphisms are more frequent in patients with AMD than in the control group, and they seem to increase the risk of suffering the disease in the population. Expand
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
  • G. Hageman, L. Hancox, +15 authors The AMD Clinical Study Group *
  • Biology, Medicine
  • Annals of medicine
  • 2006
The absence of CFHR1 and/or CFHR3 may account for the protective effects conferred by some CFH haplotypes and the high frequencies of the 402H allele and the delCFHR1/CFHR3 alleles in African populations suggest an ancient origin for these alleles. Expand
A 32 kb Critical Region Excluding Y402H in CFH Mediates Risk for Age-Related Macular Degeneration
Examination of 34 AMD-enriched extended families and controls demonstrated that deletion CNP148 was protective against AMD, independent of SNPs at CFH, and identified a 32-kb region downstream of Y402H shared by all three risk haplotypes, suggesting that this region may be critical for AMD development. Expand
Influence of CFH, HTRA1 and ARMS2 haplotype polymorphisms in the development of age-related macular disease
Haplotypes which combine “risk genotypes” are more frequent in patients with AMD than in the control group, and they seem to increase the risk of suffering the disease in the population of healthy people. Expand
Protective chromosome 1q32 haplotypes mitigate risk for age-related macular degeneration associated with the CFH-CFHR5 and ARMS2/HTRA1 loci
It is found that genetic combinations of CFH-CFHR5 haplotypes (diplotypes) strongly influence AMD susceptibility and that individuals with risk/protective diplotypes are substantially protected against the development of disease. Expand
Rare Genetic Variants Associated With Development of Age-Related Macular Degeneration.
The results suggest that genetic tests for AMD might be designed to detect common and rare genetic variants, especially in families, because rare variants contribute to the age at onset and progression of the disease. Expand


A common haplotype in the complement regulatory gene factor H (HF1/CFH) predisposes individuals to age-related macular degeneration.
It is shown that factor H (HF1), the major inhibitor of the alternative complement pathway, accumulates within drusen and is synthesized by the retinal pigmented epithelium, implicating HF1 function in the pathogenetic mechanisms underlying AMD. Expand
Hypothetical LOC387715 is a second major susceptibility gene for age-related macular degeneration, contributing independently of complement factor H to disease risk
This work analyzed 93 single nucleotide polymorphisms for allelic association with AMD in two independent case-control cohorts of German origin and found the strongest association centered over a frequent coding polymorphism, Ala69Ser, at LOC387715, strongly implicating this gene in the pathogenesis of AMD. Expand
Complement Factor H Polymorphism in Age-Related Macular Degeneration
A genome-wide screen for polymorphisms associated with age-related macular degeneration revealed a polymorphism in linkage disequilibrium with the risk allele representing a tyrosine-histidine change at amino acid 402 in the complement factor H gene. Expand
Strong association of the Y402H variant in complement factor H at 1q32 with susceptibility to age-related macular degeneration.
Using a large sample of cases and controls from a single center, we show that a T-->C substitution in exon 9 (Y402H) of the complement factor H gene is strongly associated with susceptibility toExpand
Complement Factor H Variant Increases the Risk of Age-Related Macular Degeneration
DNA resequencing of the complement factor H gene within this haplotype revealed a common coding variant that significantly increases the risk for AMD with odds ratios between 2.45 and 5.57, which likely explains ∼43% of AMD in older adults. Expand
Complement Factor H Polymorphism and Age-Related Macular Degeneration
Significant association was identified within the regulation of complement activation locus and was centered over a tyrosine-402 → histidine-402 protein polymorphism in the gene encoding complement factor H. Expand
Susceptibility genes for age-related maculopathy on chromosome 10q26.
The combination of the analyses strongly implicates PLEKHA1/LOC387715 as primarily responsible for the evidence of linkage of ARM to the 10q26 locus and as a major contributor to ARM susceptibility. Expand
De novo gene conversion in the RCA gene cluster (1q32) causes mutations in complement factor H associated with atypical hemolytic uremic syndrome
Functional significance analysis of the C3b/C3d binding characteristics of recombinant mutant S1191L/V1197A protein, heparin affinity chromatography and haemolytic assays of serum samples from aHUS patients carrying these changes showed that these changes resulted in impaired C3B binding and a defective capacity to control complement activation on cellular surfaces. Expand
An international classification and grading system for age-related maculopathy and age-related macular degeneration. The International ARM Epidemiological Study Group.
A common detection and classification system is needed for epidemiologic studies of age-related maculopathy (ARM). Such a grading scheme for ARM is described in this paper. ARM is defined as aExpand
The risk and natural course of age-related maculopathy: follow-up at 6 1/2 years in the Rotterdam study.
The absolute risk of AMD is provided as a function of age and early ARM fundus signs, and it is shown that both are prominent independent risk factors. Expand