Portal de Periódicos da CAPES

Complement Factor H Polymorphism in Age-Related Macular Degeneration

2005; American Association for the Advancement of Science; Volume: 308; Issue: 5720 Linguagem: Inglês

10.1126/science.1109557

1095-9203

Robert J. Klein, Caroline J. Zeiss, Emily Y. Chew, Jen-Yue Tsai, Richard S. Sackler, Chad Haynes, Alice K. Henning, John Paul SanGiovanni, Shrikant Mane, Susan T. Mayne, Michael B. Bracken, Frederick L. Ferris, Jürg Ott, Colin J. Barnstable, Josephine Hoh,

Retinal Imaging and Analysis

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.