Complement Factor H Polymorphism in Age-Related Macular Degeneration

• Published in: Science (American Association for the Advancement of Science) Vol. 308; no. 5720; pp. 385 - 389
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 15.04.2005; The American Association for the Advancement of Science
• Subjects: Aged; Aged, 80 and over; Aging; Alleles; Amino Acid Substitution; Amino acids; Biological and medical sciences; Blindness; C-reactive protein; Care and treatment; Case-Control Studies; Choroid - immunology; Chromosomes; Chromosomes, Human, Pair 1 - genetics; complement; Complement Factor H - chemistry; Complement Factor H - genetics; Complement Factor H - physiology; Complement Membrane Attack Complex - analysis; confidence interval; Drusen; elderly; Exons; Family studies; Female; Genes; Genetic Markers; Genetic Predisposition to Disease; Genomes; Genotype; Genotype & phenotype; Genotypes; genotyping; Haplotypes; heparin; Histidine - genetics; homozygosity; Humans; Immunity, Innate; Introns; Linkage Disequilibrium; Macular degeneration; Macular Degeneration - genetics; Magnetic fields; Male; Medical genetics; Medical sciences; Older people; Oligonucleotide Array Sequence Analysis; Ophthalmology; P values; Pigment Epithelium of Eye - immunology; Polymorphism; Polymorphism, Genetic; Polymorphism, Single Nucleotide; Proteins; Retinopathies; risk; Risk Factors; single nucleotide polymorphism; Smoking; Vision; United States; Macular degeneration; Human; Eye disease; Retinopathy; Complement; Age; Polymorphism
• ISSN: 0036-8075; 1095-9203; 1095-9203
• DOI: 10.1126/science.1109557

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.