Dataset Information

Exploring the Novel Susceptibility Gene Variants for Primary Open-Angle Glaucoma in East Asian Cohorts: The GLAU-GENDISK Study.

ABSTRACT: Primary open-angle glaucoma (POAG) can develop even within normal ranges of intraocular pressure, and this type of glaucoma (so-called 'normal-tension glaucoma [NTG]') is highly prevalent in East Asia including Korea and Japan. We conducted exome chip analysis to identify low-frequency and rare variants associated with POAG from the primary cohort (309 POAG patients and 5,400 control, all Koreans). For replication, Korean (310 POAG patients and 5,612 controls) and Japanese (565 POAG patients and 1,104 controls) cohorts were further investigated by targeted genotyping. SNP rs116121322 in LRRC27 showed nominally significant association with POAG in the discovery cohort (OR?=?29.85, P?=?2E-06). This SNP was validated in the Korean replication cohort but only in the NTG subgroups (OR?=?9.86, P?=?0.007). Japanese replication cohort did not show significant association with POAG (P?.00.44). However, the meta-analysis in the entire cohort revealed significant association of rs116121322 with POAG (ORcombined?=?10.28, Pcombined?=?1.4E-07). The LRRC27 protein expression was confirmed from human trabecular meshwork cells. For gene-based testing, METTL20 showed a significant association in POAG (Pcombined?=?0.002) and in the subgroup of NTG (Pcombined?=?0.02), whereas ZNF677 were significantly associated with only in the subgroup of high-tension glaucoma (Pcombined?=?1.5E-06). Our findings may provide further genetic backgrounds into the pathogenesis of POAG, especially for the patients who have lower baseline intraocular pressures.

SUBMITTER: Kim YW

PROVIDER: S-EPMC6959350 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Exploring the Novel Susceptibility Gene Variants for Primary Open-Angle Glaucoma in East Asian Cohorts: The GLAU-GENDISK Study.

Kim Yong Woo YW Kim Yu Jeong YJ Cheong Hyun Sub HS Shiga Yukihiro Y Hashimoto Kazuki K Song Yong Ju YJ Kim Seok Hwan SH Choi Hyuk Jin HJ Nishiguchi Koji M KM Kawai Yosuke Y Nagasaki Masao M Nakazawa Toru T Park Ki Ho KH Kim Dong Myung DM Jeoung Jin Wook JW

Scientific reports 20200114 1

Primary open-angle glaucoma (POAG) can develop even within normal ranges of intraocular pressure, and this type of glaucoma (so-called 'normal-tension glaucoma [NTG]') is highly prevalent in East Asia including Korea and Japan. We conducted exome chip analysis to identify low-frequency and rare variants associated with POAG from the primary cohort (309 POAG patients and 5,400 control, all Koreans). For replication, Korean (310 POAG patients and 5,612 controls) and Japanese (565 POAG patients and ...[more]

PMID: 31937794

Similar Datasets

Project description:PURPOSE: Glaucoma is a heterogeneous group of optic neuropathies with a complex genetic basis. To date, only the following four genes have been identified: viz. myocilin (MYOC), optineurin (OPTN), WD repeat domain 36 (WDR36), and neurotrophin 4 (NTF4). However, there are conflicting reports regarding the involvement of WDR36 in the pathogenesis of primary open-angle glaucoma (POAG). In the Asian population, mutations in WDR36 appear to play a minor role in POAG pathogenesis but polymorphic variants have been found to be associated with POAG, especially in patients with high tension glaucoma (HTG). The purpose of this study is to determine the role of WDR36 in East Indian POAG patients. To date, no other studies have yet examined this role. METHODS: Ten single nucleotide polymorphisms (SNPs; rs1971050, rs1993465, rs13153937, rs10038177, rs11241095, rs10043631, rs10038058, rs10491424, rs17553936, and rs13186912) spanning almost the entire WDR36 gene were selected and their association with eastern Indian POAG patients was evaluated. Our study pool consisted of 323 POAG patients. Of these 116 were patients who had HTG with intraocular perssure (IOP) >21mmHg and 207 were found to be non-HTG patients (presenting IOP<21mmHg). The study also included 303 participants as controls. The polymorphisms were genotyped in both the patients and the controls using the PCR-RFLP method. Moreover, the SNP that showed significant association was validated by DNA sequencing. The haplotypes were obtained using Haploview 4.1 software. The allele and haplotype frequencies were compared between the patient group and the control group using Pearson's ?(2) test. RESULTS: First, we genotyped the selected SNPs in the 323 POAG patients and 119 of the participants in the control group, in which only rs10038177 (c.710+30C>T) was found to be strongly associated with the HTG cases (OR=2.186; 95% CI=1.458-3.277; p=1.4×10(-4)). To increase the significance of the study, the SNP was genotyped in an additional 184 of the participants in the control group and it was observed that the SNP retained the association (OR=1.216; 95% CI=1.064-2.306; p=0.002). However, no haplotype was found to have any sustainable association with POAG. Based on the LD pattern and location of rs10038177, exon 5 of WDR36 was sequenced but no suspected disease-causing variant was detected. CONCLUSIONS: Our study suggests a possible association between WDR36 SNP in a cohort of eastern Indian POAG patients who also have high intraocular pressure (IOP). This study needs to be further validated in a larger patient cohort.

Dataset Information

Exploring the Novel Susceptibility Gene Variants for Primary Open-Angle Glaucoma in East Asian Cohorts: The GLAU-GENDISK Study.

Publications

Exploring the Novel Susceptibility Gene Variants for Primary Open-Angle Glaucoma in East Asian Cohorts: The GLAU-GENDISK Study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets