Analysis of LOXL1 SNPs and Glaucoma Endophenotypes: Central Corneal Thickness, Intraocular Pressure and Vertical Cup to Disc Ratio in an isolated Greek Population

Abstract

Purpose: : To determine if lysyl-oxidase-like 1 (LOXL1) gene polymorphisms are associated with the glaucoma endophenotypes, central corneal thickness (CCT), intraocular pressure (IOP) or vertical cup-to-disc ratios (CDR).

Methods: : Six hundred villagers from a small Greek village were enrolled in a clinical and genetic study, 376 of whom were linked in a single 11 generation pedigree. All participants underwent a detailed ophthalmological exam. The two LOXL1 SNPS, rs1048661 and rs3825942, were sequenced bidirectionally. Power calculations and measured genotype analysis was conducted using SOLAR version 4.2, in order to account for the relatedness between individuals.

Results: : Power calculations indicate that we had 70% power to detect an association between the LOXL1 SNPs and our phenotypes. No association was found between the LOXL1 SNPS and CCT, IOP or vertical CDR. The mean CCT was 570 µM for all three LOXL1 rs1048661 genotypes. For LOXL1 rs3825942 mean CCT was 570 µM for the AA and AB genotypes and 569 µM for the BB genotype. The mean maximum IOP for rs1048661 was 18 mm Hg for the AA and AB genotypes and 17 mm Hg for the BB genotype. The mean maximum IOP for rs3825942 was 18 mm Hg for the AA and AB genotypes and 19 mm Hg for the BB genotype. However, using a subset analysis taking into account glaucoma diagnosis revealed a significant association between rs3825942 and CCT in POAG cases (p=0.007).

Conclusions: : The LOXL1 polymorphisms rs1048661 and rs3825942 appear to not influence IOP, or vertical cup-to-disc ratio in this population, however rs3825942 is related to CCT in individuals from the cohort under investigation affected with POAG.

Clinical Trial: : www.clinicaltrials.gov NCT00788762

Keywords: genetics