Thorleifsson et al. (2007) found that a SNP in exon 1 of the LOXL1 gene, rs1048661, which corresponds to an arg-to-leu substitution at codon 141 (R141L), is associated with risk of developing exfoliation syndrome (XFS; 177650), resulting in glaucoma. The risk allele of this SNP, G, showed strong individual association in combined case-control samples from Iceland and Sweden (OR = 2.46, P = 2.3 x 10(-12)). The rs1048661 SNP was in strong linkage disequilibrium with another SNP in exon 1, rs3825942 (153456.0002). In samples of adipose tissue with genotype data for these 2 SNPs, LOXL1 expression was reduced by an estimated 7.7% with each copy carried of the G allele of rs1048661 (P = 8.3 x 10(-7)).
In a Caucasian Australian population-based cohort of 2,508 individuals, 86 (3.4%) of whom were diagnosed with pseudoexfoliation syndrome, Hewitt et al. (2008) confirmed that 2 previously identified nonsynonymous variants in exon 1 of LOXL1, R141L and G153D (153456.0002), were strongly associated with pseudoexfoliation: 2 copies of the high-risk haplotype at these SNPs conferred a risk of 7.20 (95% CI, 3.04 to 20.75) compared to no copies of the high-risk haplotype.
Lemmela et al. (2009) analyzed rs1048661 as well as 2 other LOXL1 SNPS, rs3825942 and rs2165241 (153456.0003), in a case-control study of 59 Finnish patients with XFS and 82 with exfoliation glaucoma (XFG) and a family study of 28 patients with XFS or XFG and 92 unaffected relatives from an extended Finnish family. They found significant association in both studies with the risk (G) allele of rs1048661 (p = 2.65 x 10(-5) and 0.0007, respectively). The corresponding 3-locus haplotype GGT increased the risk of XFS/XFG nearly 15-fold relative to the low-risk GAC haplotype (p = 1.6 x 10(-16)).
