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

• DOI: 10.1038/ng1890
• Publication Date: 2006-09-24T18:14:26Z
• Authors: Anne E Hughes; Nick Orr; Hossein Esfandiary; Martha Diaz-Torres; Timothy Goodship; Usha Chakravarthy
• Keywords: 0301 basic medicine; /dk/atira/pure/subjectarea/asjc/1300/1311; name=Genetics; Age Factors; 610; /dk/atira/pure/subjectarea/asjc/2700/2716; Single Nucleotide; Research Support; Polymorphism, Single Nucleotide; 3. Good health; Macular Degeneration; 03 medical and health sciences; name=Genetics(clinical); Haplotypes; Risk Factors; Case-Control Studies; Complement Factor H; Journal Article; Humans; Genetic Predisposition to Disease; Polymorphism; Non-U.S. Gov't; Gene Deletion; Aged

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 genotyped polymorphisms spanning the cluster of CFH and five CFH-related genes on chromosome 1q23 in 173 individuals with severe neovascular AMD and 170 elderly controls with no signs of AMD. Detailed analysis showed a common haplotype associated with decreased risk of AMD that was present on 20% of chromosomes of controls and 8% of chromosomes of individuals with AMD. We found that this haplotype carried a deletion of CFHR1 and CFHR3, and the proteins encoded by these genes were absent in serum of homozygotes. The protective effect of the deletion haplotype cannot be attributed to linkage disequilibrium with Y402H and was replicated in an independent sample.