Haplotype Analysis of the ARMS2/HTRA1 Region in Japanese Patients with Typical Neovascular Age-Related Macular Degeneration or Polypoidal Choroidal Vasculopathy
Haplotype Analysis of the ARMS2/HTRA1 Region in Japanese Patients with Typical Neovascular Age-Related Macular Degeneration or Polypoidal Choroidal Vasculopathy
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DOI：
10.1007/s10384-010-0865-2
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发表时间：
2010-11-01
影响因子：
2.4
通讯作者：
Yoshimura, Nagahisa
中科院分区：
文献类型：
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作者：
Gotoh, Norimoto;Yamashiro, Kenji;Yoshimura, Nagahisa
目的：比较染色体10 q26的ARMS 2/HTRA 1区域对典型新生血管性年龄相关性黄斑变性（nAMD）（也称为典型渗出性AMD）和息肉状脉络膜血管病（PCV）的基因组贡献。方法：从84名典型nAMD患者、181名PCV患者和276名对照参与者中制备DNA样本。所有的18个单倍型标记单核苷酸多态性（SNP）来自HapMap数据和潜在的功能变异，rs 11200638，延长了85.2 kb的ARMS 2/HTRA 1区域，进行基因分型。结果：在19个SNPs中，有6个与典型的nAMD和PCV有统计学显著相关（P < 1 x 10 - 3），在包含3个SNPs的片段中达到峰值：rs3793917，rs 10490924，和rs 11200638（P < 10 - 7）。从跨越33 kb的9个SNP推断出6种常见的单倍型，其中包括与两种表型相关的6个SNP。在6种常见的单倍型中，1种与典型的nAMD呈正相关，2种与PCV相关。结论：日本PCV患者ARMS 2/HTRA 1区域的关联模式和单倍型估计与日本典型nAMD患者非常相似。nAMD和PCV的多态性可能位于该区域或rs 10490924和rs 11200638的强连锁不平衡。Jpn J Ophthalmol 2010;54：609-614（C）日本眼科学会2010
Purpose: To compare the genomic contribution of the ARMS2/HTRA1 region of chromosome 10q26 to typical neovascular age-related macular degeneration (nAMD) (also known as typical exudative AMD) and to polypoidal choroidal vasculopathy (PCV).Methods: DNA samples were prepared from 84 patients with typical nAMD, 181 patients with PCV, and 276 control participants. All of the 18 haplotype-tagging single-nucleotide polymorphisms (SNPs) derived from the HapMap data and the potential functional variant, rs11200638, which extended the ARMS2/HTRA1 region by 85.2 kb, were genotyped. Associations were tested using single-SNP and haplotype analyses.Results: Statistically significant associations were found for six of the 19 SNPs with both typical nAMD and PCV (P < 1 x 10(-3)), peaking at a segment containing three of the SNPs: rs3793917, rs10490924, and rs11200638 (P < 10(-7)). Six common haplotypes were inferred from the nine SNPs spanning 33 kb, which included the six SNPs associated with both phenotypes. Among the six common haplotypes, one showed a positive association with typical nAMD, and two, including the one mentioned above, were associated with PCV. In addition, they corresponded to the risk alleles rs10490924 and rs11200638.Conclusions: The association pattern and haplotype estimation in the ARMS2/HTRA1 region of Japanese patients with PCV were very similar to those of Japanese patients with typical nAMD. The polymorphisms responsible for nAMD and PCV may be located in this region or in the strong linkage disequilibrium of rs10490924 and rs11200638. Jpn J Ophthalmol 2010;54:609-614 (C) Japanese Ophthalmological Society 2010