Complement factor H polymorphism in age-related macular degeneration.
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.
Klein
Robert J
RJ
Laboratory of Statistical Genetics, Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
Zeiss
Caroline
C
Chew
Emily Y
EY
Tsai
Jen-Yue
JY
Sackler
Richard S
RS
Haynes
Chad
C
Henning
Alice K
AK
SanGiovanni
John Paul
JP
Mane
Shrikant M
SM
Mayne
Susan T
ST
Bracken
Michael B
MB
Ferris
Frederick L
FL
Ott
Jurg
J
Barnstable
Colin
C
Hoh
Josephine
J
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D000483:Alleles; D019943:Amino Acid Substitution; D016022:Case-Control Studies; D002829:Choroid / Q000276:immunology; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D017242:Complement Factor H / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D015938:Complement Membrane Attack Complex / Q000032:analysis; D005091:Exons; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006639:Histidine / Q000235:genetics; D006801:Humans; D007113:Immunity, Innate; D007438:Introns; D015810:Linkage Disequilibrium; D008268:Macular Degeneration / Q000235:genetics*; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D010857:Pigment Epithelium of Eye / Q000276:immunology; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012907:Smoking
C493495:CFH protein, human; D015938:Complement Membrane Attack Complex; D005819:Genetic Markers; D006639:Histidine; D017242:Complement Factor H