Haplotypes in the complement factor H (CFH) gene: associations with drusen and advanced age-related macular degeneration.
BACKGROUND
Age-related macular degeneration (AMD), the leading cause of blindness in the Western world, is a complex disease that affects people over 50 years old. The complement factor H (CFH) gene has been repeatedly shown to be a major factor in determining susceptibility to the advanced form of the condition. We aimed to better understand the functional role of this gene in the AMD disease process and assess whether it is associated with earlier forms of the disease.


RESULTS
WE genotyped SNPS at the cfh gene locus in three independent populations with AMD: (a) extended families where at least 3 family members had AMD; (b) sporadic cases of advanced AMD and (c) cases from the Age-Related Eye Disease Study (AREDS). We investigated polymorphisms and haplotypes in and around the CFH gene to assess their role in AMD. CFH is associated with early/intermediate and advanced AMD in both familial and sporadic cases. In our populations, the CFH SNP, rs2274700, is most strongly associated with AMD and when incorporated into a haplotype with the Y402H SNP and rs1061147, the strongest association is observed (p<10(-9)).


CONCLUSIONS
Our results, reproduced in three populations that represent the spectrum of AMD cases, provide evidence that the CFH gene is associated with drusen as well as with advanced AMD. We also identified novel susceptibility and protective haplotypes in the AMD populations.
Francis
Peter J
PJ
Macular Degeneration Center, Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States of America. francisp@ohsu.edu
Schultz
Dennis W
DW
Hamon
Sara
S
Ott
Jurg
J
Weleber
Richard G
RG
Klein
Michael L
ML
D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D017242:Complement Factor H / Q000235:genetics*; D004311:Double-Blind Method; D005260:Female; D006239:Haplotypes; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015594:Optic Disk Drusen; D020641:Polymorphism, Single Nucleotide
D017242:Complement Factor H