purpose. The single nucleotide polymorphisms (SNPs) rs1048661, rs3825942, and rs2165241 within the LOXL1 gene were recently found to confer risk of pseudoexfoliation glaucoma (XFG) through pseudoexfoliation syndrome (XFS) in Caucasians. The purpose of this study was to test this association in Japanese subjects with XFS/XFG.

methods. Japanese subjects with clinically diagnosed XFS/XFG and normal control subjects were recruited. Genomic DNA was extracted and the three SNPs of the LOXL1 gene were genotyped by bidirectional sequencing. The association of individual SNPs with XFG/XFS was evaluated by using χ 2 and the Fisher exact test.

results. Two hundred nine Japanese patients (106 XFG and 103 XFS) and 172 control subjects were studied. Strong associations were observed for all three SNPs of LOXL1 for XFS (odds ratio [OR]= 13.56, P= 3.39× 10− 28 for allele T of rs1048661; OR= 10.71, P= 1.49× 10− 7 for allele G of rs3825942; and OR= 4.55, P= 5.33× 10− 4 for allele C of rs2165241) and XFG (OR= 25.21, P= 1.44× 10− 34 for allele T of rs1048661; OR= 11.02, P= 1.40× 10− 7 for allele G of rs3825942; and OR= 11.89, P= 4.76× 10− 6 for allele C of rs2165241). The risk-associated alleles of rs1048661 and rs2165241 differed between the Japanese and Caucasians, whereas allele G of rs3825942 was associated with disease in both populations. Conditional analysis indicated that rs3825942 was not independent but correlated highly with rs1048661. The at-risk haplotype TGC was present at an approximately two times higher rate (94.7% vs. 50.6%, P= 4.22× 10− 43) in cases than in control subjects and conferred a 2.9-fold (95% confidence interval [CI], 2.357–3.464) increased likelihood of XFS.

conclusions. Polymorphisms in the LOXL1 gene confer risk to XFS/XFG in the Japanese, but there are different risk-associated alleles and haplotypes in the Japanese.