Precis: High-risk alleles of risk-associated single-nucleotide polymorphisms (SNPs) within the lysyl oxidase-like 1 (LOXL1) gene are associated with pseudoexfoliation in patients recruited from an Irish population.
Purpose: SNPs within the LOXL1 gene have been identified as a major risk factor for pseudoexfoliation syndrome (PXF) and pseudoexfoliation glaucoma (PXFG), specifically SNPs within exon 1 and intron 1 regions of the gene. The common haplotype (G-G) of 2 SNPs within exon 1, rs1048661, and rs3825942, is the strongest associated risk factor for PXF in white populations, but is switched in some populations to act as protective or low risk. Herein, a study was undertaken to genotype an Irish population for PXF/PXFG risk-associated SNPs within LOXL1.
Materials and methods: Patient cohorts of PXFG, PXF, and controls were recruited and genotyped for risk-associated SNPs within exon 1 (rs1048661 and rs3825942), along with 3 SNPs within intron 1 (rs1550437, rs6495085, and rs6495086) of LOXL1.
Results: The risk G alleles of rs1048661 and rs3825942 were most prevalent in PXFG patients, and a significant association was found between rs3825942 and pseudoexfoliation (P=0.04). Genotypes of several intron 1 SNPs were found to be present at higher frequencies within the pseudoexfoliation patient cohort (PXF/PXFG) compared with control patients, wherein rs6495085 showed statistical association (P=0.04). The G-G-G haplotype of rs1048661, rs3825942, and rs6495085 was the most prevalent in PXFG patients compared with control patients or patients with PXF alone. Patients with the G-G-G haplotype were more likely to need surgery, suggestive of a more severe form of disease.
Conclusion: Collectively, these results represent the first study to assess the association of LOXL1 SNPs with PXFG in an Irish population.