Tang Fang Yao, Ma Li, Tam Pancy O S, Pang Chi Pui, Tham Clement C, Chen Li Jia
Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China.
Hong Kong Eye Hospital, Hong Kong, China.
Invest Ophthalmol Vis Sci. 2017 Aug 1;58(10):4384–4389. doi: 10.1167/iovs.17-22304.
This study evaluates the associations of haplotype-tagging single nucleotide polymorphisms (SNPs) in the PARL-ABCC5-HTR3D-HTR3C region with primary angle closure glaucoma (PACG), with a view to identify the responsible SNP in this region.
Thirty SNPs from the PARL-ABCC5-HTR3D-HTR3C region were genotyped in a Hong Kong Chinese cohort of 422 PACG patients and 400 control subjects, using TaqMan SNP genotyping assays. Single marker and haplotype-based association analyses were performed.
Two synonymous ABCC5 SNPs, namely rs939336 (p.Cys594=; P = 0.013; odds ratio [OR] = 1.46; 95% confidence interval [CI], 1.08 to 1.97) and rs1132776 (p.Ala395=; P = 0.009; OR = 1.47; 95% CI: 1.10 to 1.95), were associated with PACG. Mild associations were detected for ABCC5 rs9838667 (P = 0.024) and HTR3D rs12493550 (P = 0.035). Conditional analysis revealed that no SNPs remained significant after adjusting for other SNPs, suggesting none of these tagging SNPs is fully responsible for the association in this region. In subgroup analysis, ABCC5 SNPs rs939336, rs1132776, and rs983667 and HTR3D rs12493550 were associated only with the chronic form of PACG. However, these associations could not withstand the correction for multiple testing.
These findings enrich the allelic spectrum of ABCC5 in PACG. We identified no tagging SNP responsible for the association of the whole region. Further deep sequencing analysis of this region should be warranted to uncover whether there is still disease associated variant in this region.
本研究评估PARL - ABCC5 - HTR3D - HTR3C区域的单倍型标签单核苷酸多态性（SNP）与原发性闭角型青光眼（PACG）的关联，以确定该区域中起作用的SNP。
使用TaqMan SNP基因分型检测法，对香港华人队列中的422例PACG患者和400例对照受试者进行PARL - ABCC5 - HTR3D - HTR3C区域的30个SNP基因分型。进行单标记和基于单倍型的关联分析。
两个同义ABCC5 SNP，即rs939336（p.Cys594 =；P = 0.013；优势比[OR]=1.46；95%置信区间[CI]，1.08至1.97）和rs1132776（p.Ala395 =；P = 0.009；OR = 1.47；95% CI：1.10至1.95）与PACG相关。ABCC5 rs9838667（P = 0.024）和HTR3D rs12493550（P = 0.035）检测到轻度关联。条件分析显示，在对其他SNP进行校正后，没有SNP仍然显著，这表明这些标签SNP中没有一个对该区域的关联完全负责。在亚组分析中，ABCC5 SNP rs939336、rs1132776和rs983667以及HTR3D rs12493550仅与慢性形式的PACG相关。然而，这些关联无法承受多重检验校正。
这些发现丰富了PACG中ABCC5的等位基因谱。我们未发现对整个区域关联负责的标签SNP。有必要对该区域进行进一步的深度测序分析，以揭示该区域是否仍存在与疾病相关的变异。
