Role of Lysyl oxidase-like 1 gene polymorphisms in Pakistani patients with pseudoexfoliative glaucoma

Purpose: Single nucleotide polymorphisms (SNPs) rs1048661 (p.R141L) and rs3825942 (p.G153D) in the lysyl oxidaselike 1 (LOXL1) gene have been previously reported to be associated with pseudoexfoliation glaucoma (PEXG) in various Asian and European populations, but these SNPs have not yet been studied in the Pakistani population. Therefore the aim of the present study was to investigate the association of these two coding LOXL1 SNPs in Pakistani PEXG patients. Methods: One hundred twenty-eight Pakistani patients diagnosed with PEXG and 180 healthy controls were recruited for the study. Genomic DNA was extracted and both SNPs were genotyped by direct sequencing. Association of genotype and allele frequencies with PEXG were analyzed using the Chi-square (χ 2 ) test. Results: Genotype and allele frequencies of both rs1048661 and rs3825942 were found to be significantly associated with PEXG. The GG genotypes of both LOXL1 SNPs were associated with an increased risk of developing PEXG. In addition the G alleles of rs1048661 and rs3825942 confer an increased risk for PEXG with an odds ratio (OR) of 2.98 (95% CI 1.94–4.57) and OR 6.83 (95% CI 2.94–16.67), respectively. Conclusions: A significant association was found for the G allele of rs1048661 and rs3825942 in PEXG patients of Pakistani origin. Pseudoexfoliative glaucoma (PEXG) occurs when pigment and abnormal basement membrane material from the anterior segment of the eye deposit in the trabecular meshwork (TM), which raises the intraocular pressure of the eye causing a degeneration of the optic nerve. In addition the presence of pseudoexfoliative material causes changes in the cornea, camerular angle, lens and zonules as well as a significant loss in the number of axons [1,2]. The accumulation of exfoliative material in the juxtacanalicular tissue (JCT) results in the disorganization of the JCT and Schlemm’s canal followed by dysfunction of endothelial cells, which appear to be the causative factor in the development of PEXG [3]. The precise etiology and pathogenesis of pseudoexfoliative glaucoma still remains unknown. Previous molecular, biochemical and immunohistochemical studies have elucidated that proteins of the extracellular matrix (ECM), metabolism and cellular stress are differentially expressed in tissues of PEXG patients. It has been observed that the pathophysiology of PEXG involves an excessive production of elastic microfibrillar components, changes in the enzymatic cross linking processes, a proteolytic imbalance