Lysyl Oxidase-like 1 Polymorphisms and Exfoliation - Syndrome in the Japanese Population

Abstract

Purpose: : To investigate the contribution of two single-nucleotide polymorphisms (SNPs) of the lysyl oxidase-like 1 (LOXL1) gene, recently shown to be associated with exfoliation syndrome (XFS) and exfoliation glaucoma (XFG) in the Caucasian population ( Thoreleifsson et al. Science 317:1397-1400;2007, Fingert et al. Am J Ophthalmol 144:974-975; 2007, Hewitt et al, Hum Mol Genet, 2007 forthcoming) and , to the occurrence of XFS and XFG in the Japanese population.

Methods: : A total of 59 unrelated Japanese individuals with XFS, 27 XFG patients and 190 population-based controls were recruited. The SNPs rs1048661 (R141L) and rs3825942 (G153D) in the LOXL1 gene were genotyped directly. Association tests were performed for the two SNPs and inferred haplotypes.

Results: : The frequency of the G allele in rs1048661, reportedly a functional risk allele in Caucasians, existed in only 0.8% of Japanese XFS cases, but occurred with much higher frequency in controls (46.0%) and yielded a P value of 3.0 x 10^-19 and the odds ratio for the T allele in rs1048661 was 99.8 (95% CI, 13.8-722). For rs3825942, the frequency of the G allele, which is another possible risk allele in Caucasians with XFS, was 1.000 versus 0.857 in the controls (P = 1.4 x 10^-5). The most frequent haplotype in Japanese XFS patients was haplotype (T,G) (99.2%). The (G,G) haplotype, which generates the highest risk in Caucasians, was present in only a small percentage of Japanese XFS cases (0.8%).

Conclusions: : The SNPs rs1048661 and rs3825942 of the LOXL1 gene seems to be highly associated with XFS in the Japanese population, but a different polymorphism of LOXL1 may cause the development of XFS in the Japanese population.

Keywords: genetics