title: Sequence variants in HTRA1 and LOC387715/ARMS2 and phenotype and response to photodynamic therapy in neovascular age-related macular degeneration in populations from Israel.
abstract: OBJECTIVE
  Single nucleotide polymorphisms (SNPs) in the tightly linked LOC387715/ARMS2 and HTRA1 genes have been associated with age-related macular degeneration (AMD). We tested whether these SNPs are associated with AMD in Israeli populations, if they underlie variable phenotype and response to therapy in neovascular AMD (NVAMD), and if HTRA1 expression in vivo is associated with its promoter variant.
  
  
  METHODS
  Genotyping for the rs10490924 SNP in LOC387715/ARMS2 and the rs11200638 SNP in HTRA1 was performed on 255 NVAMD patients and 119 unaffected controls from Ashkenazi and Sephardic Jewish, and from Arab origins which are the main ethnic groups composing the Israeli population. Genotyping was correlated with phenotype and response to therapy among 143 patients who underwent photodynamic therapy (PDT). HTRA1 mRNA levels in white blood cells (WBCs), measured by quantitative PCR, were correlated with genotype in 27 participants.
  
  
  RESULTS
  Both SNPs were in almost complete linkage disequilibrium (D'=0.96-1). Homozygotes for the T allele of rs10490924 had an odds ratio (OR) of 8.6, with a 95% confidence interval (CI) of 3.5-20.8, and homozygotes for the A allele of rs11200638 had an OR of 10.7, with a 95% CI of 3.2-35.7, for having AMD (p<0.00001). There was no association among these SNPs and phenotype or response to PDT. HTRA1 mRNA levels in WBCs were not associated with rs11200638 genotypes.
  
  
  CONCLUSIONS
  The rs10490924 SNP in LOC387715/ARMS2 and the rs11200638 SNP in HTRA1 are strongly associated with NVAMD in this Israeli population. These variants do not have a major contribution to the variable phenotype and response to PDT which characterize NVAMD.
authors.affiliation: Department of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. chowers@hadassah.org.il
authors.forename: Itay
authors.initials: I
authors.lastname: Chowers
authors.forename: Tal
authors.initials: T
authors.lastname: Meir
authors.forename: Michal
authors.initials: M
authors.lastname: Lederman
authors.forename: Nitza
authors.initials: N
authors.lastname: Goldenberg-Cohen
authors.forename: Yoram
authors.initials: Y
authors.lastname: Cohen
authors.forename: Eyal
authors.initials: E
authors.lastname: Banin
authors.forename: Edward
authors.initials: E
authors.lastname: Averbukh
authors.forename: Itzhak
authors.initials: I
authors.lastname: Hemo
authors.forename: Ayala
authors.initials: A
authors.lastname: Pollack
authors.forename: Ruth
authors.initials: R
authors.lastname: Axer-Siegel
authors.forename: Orly
authors.initials: O
authors.lastname: Weinstein
authors.forename: Josephine
authors.initials: J
authors.lastname: Hoh
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Zack
authors.forename: Tural
authors.initials: T
authors.lastname: Galbinur
mesh_terms: D000368:Aged; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D003710:Demography; D005260:Female; D005786:Gene Expression Regulation; D005787:Gene Frequency; D005838:Genotype; D000074289:High-Temperature Requirement A Serine Peptidase 1; D006801:Humans; D007557:Israel; D007962:Leukocytes / Q000378:metabolism; D008268:Macular Degeneration / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D009389:Neovascularization, Pathologic / Q000235:genetics*; D010641:Phenotype; D010778:Photochemotherapy; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012697:Serine Endopeptidases / Q000097:blood / Q000235:genetics*
chemical_list: C514392:ARMS2 protein, human; D011506:Proteins; D012333:RNA, Messenger; D000074289:High-Temperature Requirement A Serine Peptidase 1; C474012:HTRA1 protein, human; D012697:Serine Endopeptidases