Yoshida Tsunehiko, DeWan Andrew, Zhang Hong, Sakamoto Ryosuke, Okamoto Haru, Minami Masayoshi, Obazawa Minoru, Mizota Atsushi, Tanaka Minoru, Saito Yoshihiro, Takagi Ikue, Hoh Josephine, Iwata Takeshi
National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, Japan.
Mol Vis. 2007 Apr 4;13:545-8.
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.
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.
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.
The HTRA1 promoter polymorphism, rs11200638, is a strong candidate with a functional consequence that predisposes Japanese to develop neovascular AMD.
研究10号染色体q26区域候选单核苷酸多态性（SNP）在日本人群中的作用，该区域最近在中国和白种人队列研究中显示与湿性年龄相关性黄斑变性（AMD）有关。
利用从湿性AMD患者外周血及年龄匹配的对照者中分离出的基因组DNA，我们分别对位于10号染色体q26区域、HTRA1基因上游6.6 kb处的rs10490924和上游512 bp处的rs11200638这两个SNP进行基因分型，采用温度梯度毛细管电泳（TGCE）和直接测序法。对各个SNP以及与SNP补体因子H（CFH）Y402H联合进行关联测试。
rs10490924和rs11200638这两个SNP处于完全连锁不平衡状态（D' = 1）。先前在17个物种间进行的序列比较显示，包含rs11200638的基因组区域高度保守，而rs10490924周围区域则不然。rs11200638的等位基因关联测试得到的p值<10^(-11)。SNP rs11200638以常染色体隐性方式赋予疾病风险：对于携带两个风险等位基因拷贝的个体，经SNP CFH 402校正后的优势比为10.1（95%可信区间4.36, 23.06），而对于仅携带一个风险等位基因的个体，该比值与1无显著差异。
HTRA1启动子多态性rs11200638是一个强有力的候选因素，其功能性后果使日本人易患新生血管性AMD。
