Identification of COL11A1 single-gene polymorphisms in patients with primary angle-closure glaucoma

Abstract

Introduction: According to a survey of the Rapid Assessment of Avoidable Blindness (RAAB) in Vietnam in 2015, glaucoma is the third most common cause of blindness after cataracts and fundus diseases, with a rate of 4%. Worldwide, studies on primary angle-closure glaucoma (PACG) have revealed approximately 50 genes and many related gene variants. In primary angle-closure glaucoma, COL11A1 was identified as one of the eight genes with the most important role related to the disease. There have been many studies analyzing gene mutations associated with eye diseases in Vietnam, but few studies have been conducted on PACG. Therefore, we focused on detecting some gene variants of COL11A1 in patients with PACG in several military hospitals.

Methods: Blood samples from 30 patients with primary angle-closure glaucoma were clinically evaluated. Total DNA was extracted from the samples using a mixture of phenol, chloroform, and isoamyl alcohol (PCI). Primer design to multiply COL11A1 gene segments based on reference gene sequences published on NCBI. The designed gene fragment was amplified by PCR on a thermocycler. After electrophoresis on a 1% agarose gel, the PCR products were purified using GenJET PCR purification kits according to the manufacturer's instructions. Gene sequencing was performed by Sanger sequencing. The obtained sequences were processed and compared with published sequences in the International Gene Data Bank using BioEdit software.

Results: In 12/30 patients, the rs12138977 (C>T) variant of the COL11A1 gene, which is a mutation in the intron region, was detected. The rs12138977 variant is thought to be related to disease severity. In the exon region of the COL11A1 gene, the rs1676486 (A>G) variant was detected in 21/30 patient samples. At the mutation site, the Ser residue at position 1535 changes to a Pro.

Conclusion: Although we have identified some alterations in COL11A1 genes, further investigation is needed to understand the underlying mechanisms and patient-specific and clinical manifestations associated with these variants. These findings contribute to the understanding of the genetic basis of primary angle-closure glaucoma, with the hope of supporting the diagnosis and treatment of this disease in Vietnam.