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Complement Factor H Polymorphism in Age-Related Macular Degeneration

Robert J. KleinNational Eye Institute, Building 10, CRC, 10 Center Drive, Bethesda, MD 20892-1204, USACaroline J. ZeissLaboratory of Statistical Genetics, Rockefeller University, 1230 York Avenue, New York, NY 10021, USAEmily Y. ChewNational Eye Institute, Building 10, CRC, 10 Center Drive, Bethesda, MD 20892-1204, USAJen-Yue TsaiNational Eye Institute, Building 10, CRC, 10 Center Drive, Bethesda, MD 20892-1204, USARichard S. SacklerNational Eye Institute, Building 10, CRC, 10 Center Drive, Bethesda, MD 20892-1204, USAChad HaynesDepartment of Ophthalmology and Visual Science, Yale University School of Medicine, 330 Cedar Street, New Haven, CT 06520, USAAlice K. HenningBiological Imaging Core, National Eye Institute, 9000 Rockville Pike, Bethesda, MD 20892, USAJohn Paul SanGiovanniNational Eye Institute, Building 10, CRC, 10 Center Drive, Bethesda, MD 20892-1204, USAShrikant ManeDepartment of Ophthalmology and Visual Science, Yale University School of Medicine, 330 Cedar Street, New Haven, CT 06520, USASusan T. MayneBiological Imaging Core, National Eye Institute, 9000 Rockville Pike, Bethesda, MD 20892, USAMichael B. BrackenNational Eye Institute, Building 10, CRC, 10 Center Drive, Bethesda, MD 20892-1204, USAFrederick L. FerrisLaboratory of Statistical Genetics, Rockefeller University, 1230 York Avenue, New York, NY 10021, USAJürg OttNational Eye Institute, Building 10, CRC, 10 Center Drive, Bethesda, MD 20892-1204, USAColin J. BarnstableLaboratory of Statistical Genetics, Rockefeller University, 1230 York Avenue, New York, NY 10021, USAJosephine HohBiological Imaging Core, National Eye Institute, 9000 Rockville Pike, Bethesda, MD 20892, USA

2005en

ABI

Annotatsiya

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.

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DOI: 10.1126/science.1109557

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