Association of LOXL1 Gene Polymorphisms in Chinese Patients With Pseudoexfoliation Syndrome

Abstract

Purpose: : Single nucleotide polymorphisms (SNPs) rs1048661 and rs3825942 within the Lysyl Oxidase Like-1 (LOXL1) gene were found to confer risk to pseudoexfoliation glaucoma (XFG) through pseudoexfoliation syndrome (XFS) in Nordic, Caucasian and in two Asiatic populations (Indian and Japanese). The reported prevalence (0.3-0.7%) of XFS in the Chinese is considerably lower compared to Nordic populations. The aim of this study was to test the LOXL1 association in Chinese subjects with XFS/XFG.

Methods: : Chinese subjects with clinically diagnosed XFS/XFG and normal controls were recruited and the 2 SNPs of LOXL1 gene were genotyped by bi-directional sequencing. Allele and genotype frequencies were compared between cases and unrelated controls using PLINK. Haplotype association analysis was done with WHAP package.

Results: : 62 Chinese patients (17 XFG and 45 XFS) and 171 controls were studied. The G allele of SNP rs3825942 of LOXL1 was moderately associated (OR=10.97, P=0.0018) with pseudoxfoliation in the Chinese. The frequency of the G allele of rs1048661 was not significantly different in cases compared to controls (P=0.142) in the allelic association test. However, the genotype test showed marginal association for rs rs1048661 (P=0.0304). Only three haplotypes were observed (T-G, G-G and G-A), with G-G as a risk haplotype (P=0.0033) and G-A as a protective haplotype (P=0.00039). T-G which was a risk haplotype in the Japanese was not associated with pseudoxfoliation in the Chinese (P=0.124).

Conclusions: : Polymorphisms in the LOXL1 gene confer risk to XFS/XFG in the Chinese. However the low population prevalence of XFS in the Chinese suggests additional genetic or environmental factors to have a major influence on the phenotypic expression of XFS. The G allele of rs3825942 has been shown to be associated with XFS/XFG in all population studied to date.

Keywords: anterior segment • gene/expression • gene screening