Lysyl Oxidase‐Like 1 gene haplotypes and their association with pseudoexfoliation glaucoma in the Spanish population

Abstract

AbstractPurpose To investigate the potential association of genetic variants across the lysyl oxidase‐like 1 (LOXL1) gene in Spanish patients with Pseudoexfoliation Glaucoma (XFG).Methods A case‐control study of 105 unrelated individuals from Spain with XFG and 200 unrelated healthy controls matched by age and ethnicity were enrolled. A region of 39,230 bp‐long of genomic DNA covering the entire LOXL1 gene and regulatory regions were sequenced in 99 patients using next generation sequencing. Variant frequencies were compared with those reported from the HapMap CEU study. Restriction fragment–length polymorphism (RFLP) analysis was conducted to genotype five SNPs in the LOXL1 gene (rs16958477, rs1048661, rs3825942, rs2165241 and rs3522) in all controls and in 6 XFG patients. A case‐control association study was performed using the HaploView 4.0 software.Results The allelic frequency analysis of the five selected LOXL1 SNPs revealed that (with the exception of rs3522) they were significantly associated with an increased risk for XFG. The haplotypes CGGT and AGGT, which carry the risk alleles of rs1048661, rs3825942, and rs2165241 were significantly associated with XFG. In contrast, the haplotypes ATGC and AGAC were found to be protective.Conclusion This study confirms that common genetic variants in the LOXL1 gene are associated with XFG in the Spanish population. To our knowledge this is the first study to demonstrate this association in a population of Western Europe.