title: HTRA1 promoter polymorphism predisposes Japanese to age-related macular degeneration.
abstract: OBJECTIVE
  To study the effect of candidate single nucleotide polymorphisms (SNPs) on chromosome 10q26, recently shown to be associated with wet age-related macular degeneration (AMD) in Chinese and Caucasian cohorts, in a Japanese cohort.
  
  
  METHODS
  Using genomic DNA isolated from peripheral blood of wet AMD cases and age-matched controls, we genotyped two SNPs, rs10490924, and rs11200638, on chromosome 10q26, 6.6 kb and 512 bp upstream of the HTRA1 gene, respectively, using temperature gradient capillary electrophoresis (TGCE) and direct sequencing. Association tests were performed for individual SNPs and jointly with SNP complement factor H (CFH) Y402H.
  
  
  RESULTS
  The two SNPs, rs10490924 and rs11200638, are in complete linkage disequilibrium (D'=1). Previous sequence comparisons among seventeen species revealed that the genomic region containing rs11200638 was highly conserved while the region surrounding rs10490924 was not. The allelic association test for rs11200638 yielded a p-value <10(-11). SNP rs11200638 conferred disease risk in an autosomal recessive fashion: Odds ratio was 10.1 (95% CI 4.36, 23.06), adjusted for SNP CFH 402, for those carrying two copies of the risk allele, whereas indistinguishable from unity if carrying only one risk allele.
  
  
  CONCLUSIONS
  The HTRA1 promoter polymorphism, rs11200638, is a strong candidate with a functional consequence that predisposes Japanese to develop neovascular AMD.
authors: National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, Japan.
authors: Tsunehiko
authors: T
authors: Yoshida
authors: Andrew
authors: A
authors: DeWan
authors: Hong
authors: H
authors: Zhang
authors: Ryosuke
authors: R
authors: Sakamoto
authors: Haru
authors: H
authors: Okamoto
authors: Masayoshi
authors: M
authors: Minami
authors: Minoru
authors: M
authors: Obazawa
authors: Atsushi
authors: A
authors: Mizota
authors: Minoru
authors: M
authors: Tanaka
authors: Yoshihiro
authors: Y
authors: Saito
authors: Ikue
authors: I
authors: Takagi
authors: Josephine
authors: J
authors: Hoh
authors: Takeshi
authors: T
authors: Iwata
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D015331:Cohort Studies; D017242:Complement Factor H / Q000235:genetics; D017124:Conserved Sequence; D005260:Female; D018628:Gene Dosage; D005808:Genes, Recessive; D020022:Genetic Predisposition to Disease; D005838:Genotype; D000074289:High-Temperature Requirement A Serine Peptidase 1; D006639:Histidine; D006801:Humans; D015810:Linkage Disequilibrium; D008268:Macular Degeneration / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012697:Serine Endopeptidases / Q000235:genetics*; D014443:Tyrosine
chemical_list: C493495:CFH protein, human; D014443:Tyrosine; D006639:Histidine; D017242:Complement Factor H; D000074289:High-Temperature Requirement A Serine Peptidase 1; C474012:HTRA1 protein, human; D012697:Serine Endopeptidases