Complement Factor H Polymorphism and Age-Related Macular Degeneration

• DOI: 10.1126/science.1110189
• Publication Date: 2005-03-11T03:02:01Z
• Authors: Albert O. Edwards; Robert Ritter; Kenneth J. Abel; Alisa Manning; Carolien Panhuysen; Lindsay A. Farrer
• Keywords: Male; Genotype; Homozygote; Genetic Variation; Middle Aged; Linkage Disequilibrium; Macular Degeneration; 03 medical and health sciences; 0302 clinical medicine; Amino Acid Substitution; Gene Frequency; Haplotypes; Chromosomes, Human, Pair 1; Case-Control Studies; Complement Factor H; Humans; Female; Genetic Predisposition to Disease; Histidine; Complement Activation; Alleles; Aged

Age-related macular degeneration (AMD) is a common, late-onset, and complex trait with multiple risk factors. Concentrating on a region harboring a locus for AMD on 1q25-31, the ARMD1 locus, we tested single-nucleotide polymorphisms for association with AMD in two independent case-control populations. Significant association ( P = 4.95 × 10 -10 ) was identified within the regulation of complement activation locus and was centered over a tyrosine-402 → histidine-402 protein polymorphism in the gene encoding complement factor H. Possession of at least one histidine at amino acid position 402 increased the risk of AMD 2.7-fold and may account for 50% of the attributable risk of AMD.