Common Sequence Variants in the LOXL1 Gene Are Associated With Pigment Dispersion Syndrome and Pigmentary Glaucoma

Abstract

Purpose: : Single nucleotide polymorphisms (SNPs) within the LOXL1 gene was recently found strongly associated with pseudoesfoliation syndrome and pseudoesfoliation glaucoma. The aim of this study is to identify the presence of sequence variants of LOXL1 associated with pigment dispersion syndrome (PDS) and pigmentary glaucoma (PG).

Methods: : A cohort of 73 unrelated and clinically well characterized patients with PDS (29) and PG (44) and 150 matched healthy control subjects of Caucasian origin were included in the study. The criteria for diagnosis of PDS were as follows: open angle at gonioscopy, trabecular meshwork pigmentation, presence of Krukemberg spindle and midperipheral iris transillumination. Subjects with PG were defined as those with PDS with documented history of IOP>24, optic disc and visual field damage. Genomic DNA from whole blood was extracted using QIAamp DNA Blood Mini Kit (QIAGEN Inc., Valencia, CA). The whole LOXL1 gene was amplified by polymerase chain reaction (PCR) and sequenciated to identify single nucleotide polymorphisms. Haplotypes were generated from the genotype data and haplotype analysis was performed with UNPHACED software (Frank Dudbridge, MRC Human Genome Mapping Project Resource Centre Hinxton, Cambridge, UK). Expression levels of LOXL1 were verified on c-DNA from peripheral blood lymphocytes by quantitative real-time RT-PCR.

Results: : The combined effect of LOXL-1 SNPs shows a significant statistic association with PDS/PG (p=0.00001461). The presence of risk haplotype results in a marked decrease of expression level of LOXL1 (Mean of 1/2 ^-ΔΔCT= 2.353762).

Conclusions: : The complete sequencing of LOXL1 allowed to find a defined sequence of SNPs strongly associated to pigmentary phenotype (OR=3.2). The results suggest a critical role of LOXL1 gene in the pathogenesis of PDS/PG.

Keywords: genetics • gene/expression