LOXL1 Polymorphism Prevalence in a North Carolina Population With Exfoliation Glaucoma

Abstract

Purpose: : To determine the prevalence the recently described LOXL1 (lysyl oxidase-like 1) polymorphisms in a US Caucasian patient population with exfoliation glaucoma (XFG).

Methods: : All individuals underwent complete ocular examinations by board certified Ophthalmologists. Informed consent obtained from all participants and both control and XFG individuals were distinguished using standard clinical examination techniques and. Thirteen SNPs that tag the LOXL1 gene were genotyped using TaqMan allelic discrimination assays. Moreover, the coding region of exon 1 (that includes the previously associated SNP rs1048661) was sequenced. Allele and genotype frequencies were compared between cases and unrelated controls.

Results: : Fifty affected and 235 control individuals were recruited into the study. The previously reported association of three SNPs (rs1048661, rs2165241, and rs3825942) was replicated in our independent XFG population (single SNP p-values 0.001 to 0.02). The risk alleles at these three and several other intragenic SNPs are part of an extended XFG-associated LOXL1 haplotype. The rs3825942 SNP demonstrates a 100% sensitivity (49 of 49 cases have the G allele) but only 3.1% specificity (7 of 225 controls lack the G allele).

Conclusions: : We have replicated the association of LOXL1 and XFG in a US patient population that confirms the strong association previously reported for Icelandic and Swedish samples. Although the sensitivity of LOXL1 SNPs is very high, we found the specificity to be very low. Therefore, this association should not be the sole basis of a diagnostic test for XFG. It is likely that additional genetic or environmental factors influence the development of XFG.

Keywords: genetics • candidate gene analysis • gene screening