Complement factor H polymorphism in age-related macular degeneration

RJ Klein, C Zeiss, EY Chew, JY Tsai, RS Sackler… - Science, 2005 - science.org
RJ Klein, C Zeiss, EY Chew, JY Tsai, RS Sackler, C Haynes, AK Henning, JP SanGiovanni
Science, 2005science.org
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 …
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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