COL11A1 Polymorphisms Are Associated with Primary Angle-Closure Glaucoma Severity.

Yani Wan,Li Tang,Wenjun Cao,Yanting Gao,Shengjie Li,Xinghuai Sun

doi:10.1155/2019/2604386

Abstract

Purpose PLEKHA7 and COL11A1 were genotyped for single-nucleotide polymorphisms (SNPs) to investigate the possible association of these two genes with primary angle-closure glaucoma (PACG) and disease severity. Method A total of 51 PACG cases and 51 normal controls were recruited. Twelve SNPs in the PLEKHA7 (rs216489, rs1027617, rs366590, rs11024060, rs6486330, rs11024097, and rs11024102) and COL11A1 (rs1676484, rs3753841, rs12138977, rs2126642, and rs2622848) genes were genotyped by direct Sanger sequencing. Distributions of allele frequencies and genotype frequencies in cases and controls, as well as in mild, moderate, and severe subgroups, were compared based on mean defect (MD ≤ 6.00 dB, 6 dB < MD ≤ 12 dB, and MD > 12 dB were considered mild, moderate, and severe, respectively). Independent Student's t-tests and chi-square tests were used to compare characteristics of PACG cases and controls. Chi-square tests were used to compare the distribution of allele frequencies in cases and controls and in MD-based subgroups with various degrees of glaucoma severity. Binary logistic regression was used to compare the distribution of genotype frequencies and calculate odds ratios (OR) with confidence intervals (CI). Result Three of the 12 SNPs in COL11A1, rs1676486 (P=0.026, OR = 2.089, 95% CI = 1.092–3.996), rs3753841 (P=0.036, OR = 1.886, 95% CI = 1.038–3.426), and rs12138977 (P=0.024, OR = 2.133, 95% CI = 1.104–4.123) were found to have a significant association with PACG. Furthermore, in the subgroup analysis, rs1676486 (P=0.018, OR = 2.416, 95% CI = 1.284–4.544; P=0.011, OR = 2.119, 95% CI = 1.204–3.729), rs12138977 (P=0.009, OR = 2.158, 95% CI = 1.287–3.618; P=0.006, OR = 1.962, 95% CI = 1.239–3.106), and rs3753841 (P=0.007, OR = 2.550, 95% CI = 1.344–4.839) showed statistically significant differences between moderate/severe groups and controls. Conclusion Our data suggested that COL11A1 rs1676484, rs3753841, and rs12138977 polymorphisms may be of value for further study as potential gene-dependent risk factors for developing PACG. Moreover, COL11A1 rs1676484 and rs12138977 polymorphisms might be associated with PACG disease severity.

Highlights

Primary angle-closure glaucoma (PACG) is a neurodegenerative disease characterized by elevated intraocular pressure (IOP) due to a mechanical obstruction of the trabecular meshwork by either apposition of the peripheral iris to the trabecular meshwork or a synechial closed angle [1]
COL11A1 is located on chromosome 1p21, comprises 68 exons, and is approximately 250 kb in length [5]. Pathogenic mutations in this gene can result in type II Stickler syndrome and Marshall syndrome [6, 7], while rs1676486 on COL11A1 is associated with lumbar disc herniation susceptibility [8]
Pleckstrin homology domain-containing family A member 7 (PLEKHA7) is an adherens junction protein [9] required for organizing the epithelial architecture and contributes to tissue homeostasis

Summary

Introduction

Primary angle-closure glaucoma (PACG) is a neurodegenerative disease characterized by elevated intraocular pressure (IOP) due to a mechanical obstruction of the trabecular meshwork by either apposition of the peripheral iris to the trabecular meshwork or a synechial closed angle [1]. Genome-wide association studies (GWAS) have recently identified several new PACG loci and genes, including PLEKHA7, COL11A1, EPDR1, CHAT, GLIS3, FERMT2, and DPM2-FAM102 A, which may shed light on the molecular mechanisms of PACG [3, 4]. Pleckstrin homology domain-containing family A member 7 (PLEKHA7) is an adherens junction protein [9] required for organizing the epithelial architecture and contributes to tissue homeostasis Since it is likely involved in regulating fluid flow across the inner wall of the Schlemm’s canal [10], it was proposed that mutations in this gene could affect fluid dynamics in the pathophysiology of angle-closure glaucoma [11]

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Results

Conclusion