Complement Factor H Polymorphism in Age-Related Macular Degeneration
Year of Publication
Klein, RJ; Zeiss, C; Chew, EY; Tsai, JY; Sackler, RS; Haynes, C; Henning, AK; SanGiovanni, JP; Mane, SM; Mayne, ST; Bracken, MB; Ferris, FL; Ott, J; Barnstable, C; Hoh, J
aging; Alleles; Amino Acid Substitution; Case-Control Studies; Choroid; Chromosomes- Human- Pair 1; Complement Factor H/Membrane Attack Complex; Exons; Genetic Markers; Genetic Predisposition to Disease; Genotype; Haplotypes; Histidine; Immunity-Innate
Age-related macular degeneration (AMD) is a major cause of blindness in the elderly. We report a genome-wide screen of 96 cases and 50 controls for polymorphisms associated with AMD. Among 116,204 single-nucleotide polymorphisms genotyped, an intronic and common variant in the complement factor H gene (CFH) is strongly associated with AMD (nominal P value <10(-7)). In individuals homozygous for the risk allele, the likelihood of AMD is increased by a factor of 7.4 (95% confidence interval 2.9 to 19). Resequencing revealed a polymorphism in linkage disequilibrium with the risk allele representing a tyrosine-histidine change at amino acid 402. This polymorphism is in a region of CFH that binds heparin and C-reactive protein. The CFH gene is located on chromosome 1 in a region repeatedly linked to AMD in family-based studies.