Complement factor H polymorphism in age-related macular degeneration.

Publication Type
Journal Article
Year of Publication
Klein, Robert J; Zeiss, Caroline; Chew, Emily Y; Tsai, Jen-Yue; Sackler, Richard S; Haynes, Chad; Henning, Alice K; Sangiovanni, John Paul; Mane, Shrikant M; Mayne, Susan T; Bracken, Michael B; Ferris, Frederick L; Ott, Jurg; Barnstable, Colin; Hoh, Josephine
Date Published
2005 Apr 15
Aged; Aged, 80 and over; aging; Alleles; Amino Acid Substitution; Case-Control Studies; Choroid; Chromosomes, Human, Pair 1; Complement Factor H; Complement Membrane Attack Complex; Exons; Female; Genetic Markers; Genetic Predisposition to Disease; Genotype; Haplotypes; Histidine; Humans; Immunity, Innate; Introns; Linkage Disequilibrium; Macular Degeneration; Male; Oligonucleotide Array Sequence Analysis; Pigment Epithelium of Eye; Polymorphism, Genetic; Polymorphism, Single Nucleotide; Risk Factors; Smoking

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.