Association of Loxl1 Common Sequence Variants in German and Italian Patients With Pseudoexfoliation Syndrome

Abstract

Purpose: : Three common sequence variants in lysyl oxidase-like 1 (LOXL1) gene were recently associated both with pseudoexfoliation (PEX) and pseudoexfoliation glaucoma (PEXG) in populations from Iceland and Sweden. In this study, we investigated genetic association of these variants in PEX and PEXG patients of German and Italian descent.

Methods: : The three LOXL1 single-nucleotide polymorphisms (SNPs), one intronic (rs2165241) and two non synonymous coding SNPs (rs1048661: R141L and rs3825942: G153D) were genotyped in a total of 726 unrelated PEX /PEXG patients (517 Germans and 209 Italians) and 418 healthy subjects who had repeated normal ophthalmologic examinations and a genetic association study was performed.

Results: : Strong association with the three LOXL1 common sequence variants was seen in both PEX and PEXG glaucoma patients groups independent of their geographic origin (rs2165241, combined OR = 3.26, P = 6.77x10^-30; rs1048661, OR=2.49, P=4.32x10^-16; rs3825942, OR=3.26, P=1.21x10^-11). Similarly, homozygosity for the frequent haplotype composed of the two coding SNPs (rs1048661 and rs3825942) was strongly associated with disease (G-G, OR = 3.58, P = 5.21 10^-43).

Conclusions: : Genetic variants in LOXL1 confer risk to PEX in German and Italian populations, independently of the presence of secondary glaucoma, confirming findings in patients from Northern Europe.

Keywords: anterior segment • clinical (human) or epidemiologic studies: risk factor assessment • genetics