Chowers Itay, Meir Tal, Lederman Michal, Goldenberg-Cohen Nitza, Cohen Yoram, Banin Eyal, Averbukh Edward, Hemo Itzhak, Pollack Ayala, Axer-Siegel Ruth, Weinstein Orly, Hoh Josephine, Zack Donald J, Galbinur Tural
Department of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
Mol Vis. 2008;14:2263-71. Epub 2008 Dec 8.
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.
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.
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.
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.
紧密连锁的LOC387715/ARMS2和HTRA1基因中的单核苷酸多态性（SNP）与年龄相关性黄斑变性（AMD）相关。我们测试了这些SNP在以色列人群中是否与AMD相关，它们是否是新生血管性AMD（NVAMD）中可变表型和对治疗反应的基础，以及体内HTRA1表达是否与其启动子变异相关。
对255例NVAMD患者以及119名未受影响的对照进行基因分型，这些对照来自构成以色列人口的主要种族群体，即阿什肯纳兹犹太人和西班牙裔犹太人以及阿拉伯人。对143例接受光动力疗法（PDT）的患者，将基因分型与表型及治疗反应进行关联分析。通过定量PCR测量27名参与者白细胞（WBC）中的HTRA1 mRNA水平，并将其与基因型进行关联分析。
两个SNP几乎完全处于连锁不平衡状态（D'=0.96 - 1）。rs10490924的T等位基因纯合子患AMD的优势比（OR）为8.6，95%置信区间（CI）为3.5 - 20.8；rs11200638的A等位基因纯合子患AMD的OR为10.7，95%CI为3.2 - 35.7（p<0.00001）。这些SNP与表型或对PDT的反应之间没有关联。WBC中的HTRA1 mRNA水平与rs11200638基因型无关。
在这个以色列人群中，LOC387715/ARMS2中的rs10490924 SNP和HTRA1中的rs11200638 SNP与NVAMD密切相关。这些变异对NVAMD的可变表型和对PDT的反应没有主要贡献。
