The Rs16958477 SNP in the Promoter Region of the LOXL1 Gene is Associated With the LOXL1 Gene Expression Level

Abstract

Purpose: : It has been reported that 2 SNPs (rs1048661 and rs3825942) in the exon 1 of lysyl oxidase-like 1 (LOXL1) gene are strongly associated with exfoliation glaucoma (XFG). However, since these SNPs can not completely explain the occurrence of XFG, there seem to be other regions which would more correspond to the occurrence of the XFG. The purpose of this study is to explore such XFG-susceptible regions in the LOXL1 promoter and examine whether they have any effects on the expression of the LOXL1 gene.

Methods: : Ninety-five Japanese XFG patients and 190 Japanese healthy control subjects were recruited. By direct sequencing analysis, genetic polymorphisms were explored in the promoter region of the LOXL1 gene. Also, the discovered polymorphic region was cloned into a reporter vector and promoter activity was assayed using the Dual Luciferase® Assay System in human primary cultured fibroblast cells.

Results: : One SNP (rs16958477) was found to be associated with XFG in the promoter region of the LOXL1 gene. The frequency of A allele as well as that of AA genotype at this SNP site were found to be significantly higher in the XFG patients than in the controls (p=2.1x10^-5 and 1.1x10^-5, respectively). An 846bp fragment of the LOXL1 promoter, harboring an A or C allele at this SNP, was cloned into a reporter vector (pGL3-basic) and used for a luciferase assay. The LOXL1 promoter with C allele at this SNP demonstrated significantly higher promoter activities than that with A allele (p<0.001).

Conclusions: : The rs16958477 SNP seems to play an important role in the occurrence of XFG through the alteration of the LOXL1 gene expression level.

Keywords: gene/expression • genetics