title: Deletion of CFHR3 and CFHR1 genes in age-related macular degeneration.
abstract: Age-related macular degeneration (AMD) impairs vision for approximately 7.5 million Americans. Both susceptibility variants and protective haplotypes in the complement factor H (CFH) gene modulate risk for AMD. Recently, deletion of the 'CFH-related' genes CFHR1 and CFHR3 was found to be segregating with a particular CFH haplotype, which reduced the risk of AMD. We tested the deletion for association in a Caucasian population of 780 cases and 265 controls and examined its effect in the context of known AMD risk factors. The deletion did not segregate perfectly with any one SNP, as previously suggested. CFH haplotype P2 was the most frequent haplotype in deletion homozygotes (47%), and the majority (14/16) of these individuals were homozygous for the non-risk allele of Y402H. Overall, deletion homozygosity was significantly more frequent in controls than cases (2.6% controls, 0.8% cases, P = 0.025, OR = 0.29, 95% CI = 0.10-0.86). After controlling for age, Y402H, smoking and LOC387715 A69S, the protective effect of the deletion was no longer statistically significant (P = 0.27). However, using a CFH haplotype that all deletion homozygotes share as a surrogate for the deletion, this marker remained modestly associated with AMD after adjustment for known risk factors (OR = 0.63, 95% CI 0.39-1.04, P = 0.07). Therefore, deletion of CFHR1 and CFHR3 may account for a small portion of the protection from AMD associated with particular haplotypes in CFH. The presence of protective haplotypes in CFH that do not carry the deletion, suggests that other protective variants in this region have yet to be discovered.
authors: Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
authors: Kylee L
authors: KL
authors: Spencer
authors: Michael A
authors: MA
authors: Hauser
authors: Lana M
authors: LM
authors: Olson
authors: Silke
authors: S
authors: Schmidt
authors: William K
authors: WK
authors: Scott
authors: Paul
authors: P
authors: Gallins
authors: Anita
authors: A
authors: Agarwal
authors: Eric A
authors: EA
authors: Postel
authors: Margaret A
authors: MA
authors: Pericak-Vance
authors: Jonathan L
authors: JL
authors: Haines
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D001483:Base Sequence; D001798:Blood Proteins / Q000235:genetics*; D002878:Chromosomes, Human, Pair 1; D003180:Complement C3b Inactivator Proteins / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008268:Macular Degeneration / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide
chemical_list: D001798:Blood Proteins; C517621:CFHR1 protein, human; C105970:CFHR3 protein, human; D003180:Complement C3b Inactivator Proteins