Lack of Association Between Polymorphisms of Elastin and Pseudoexfoliation Glaucoma

Abstract

Purpose: : Pseudoexfoliation syndrome (PXF) is a major cause of glaucoma. LOXL1 has been strongly associated with PXF in many populations including our study of U.S. clinic-based population with broad ethnic diversity. However, the risk haplotype of LOXL1 is also prevalent in control samples and is much higher than the disease prevalence in some populations such as Australian and Chinese. These results suggest that additional genetic and/or environmental factors could influence the development of this complex disease. LOXL1 catalyzes the polymerization of tropoelastin to form the mature elastin polymer. LOXL1 is also involved in elastin homeostasis and renewal, and participates in spatially organizing elastogenesis at sites of elastin deposition. These findings suggest that elastin might be involved in the pathogenesis of PXF. In the present study, we evaluated the association of elastin (ELN) with PXF.

Methods: : Three tagging SNPs which capture the majority of alleles in ELN (rs2071307, rs3823879 and rs3757587) were genotyped in 178 Caucasian patients with PXF and 113 controls. Single-SNP and haplotype association were analyzed using chi-squared test. Interaction between ELN and LOXL1 was analyzed using logistic regression.

Results: : All three ELN tagging SNPs were not significantly associated with PXF (p > 0.25). The minor allele frequencies in PXF and controls were 40.7% and 45.6% respectively for rs2071307, 6.7% and 5.4% for rs3823879, and 14.8% and 13.6% for rs3757587. Haplotype analysis showed no association between ELN and PXF (p > 0.74). Logistic regression modeling revealed no interaction effects between ELN and LOXL1 (p > 0.55).

Conclusions: : Our results suggest that the polymorphisms of ELN are not associated with PXF in Caucasian populations. Further studies are required to identify secondary genetic factors that contribute to pseudoexfoliation and associated glaucoma.

Keywords: genetics • candidate gene analysis