Lysyl Oxidase-Like 1

Alternative Names

  • LOXL1
  • LOXL

Associated Diseases

Exfoliation Syndrome
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OMIM Number

153456

Gene Map Locus
15q24.1

Description

LOXL1 belongs to the heterogeneous lysyl oxidase family of extracellular enzymes. Among other functions, they are involved in the oxidative deamination of lysine residues of tropoelastin resulting in the cross-linking of collagen and elastin fibres. They, thus, play a crucial role in the maintenance of elastic fibres, serving as both a crosslinking enzyme and an element of the scaffold to ensure spatially defined elastin deposition.

Mutations in LOXL1 have been associated with Pseudoexfoliation Syndrome (XFS), an age related systemic disorder characterized by the deposition of grayish-white amyloid like protein fibres in the anterior segment of the eye.

Molecular Genetics

The LOXL1 gene is located on the long arm of chromosome 15. It has 9 exons and spans a length of about 26 Kb. The LOXL1 protein contains 574 amino acids and is around 63 kDa in size.

Various SNPs in LOXL1 have been reported to be associated with XFS. These include the G alleles of two nonsynonymous SNPs: rs1048661 resulting in R141L and rs3825942 which results in G153D substitution. These SNPs are both in exon 1 and have been found to correspond to changes in the LOXL1 N-terminal propeptide and were predicted to affect the protein’s catalytic activity and substrate binding. The SNP rs2165241, resulting in a C-T change in intron 1 has also been associated with XFS.

Epidemiology in the Arab World

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Other Reports

Saudi Arabia
Abu-Amero et al. (2010) studied the association of LOXL1 mutations with pseudoexfoliation glaucoma (PEG) in the Saudi Arabian population. Ninety three PEG patients and 101 healthy ethnically-matched controls were recruited. DNA from the patients and controls were isolated and the entire LOXL1 sequence was analyzed. Allele frequencies were compared using the chi-square test and allelic association p values were calculated after adjusting for deviation from Hardy Weinberg equilibrium. The G allele frequencies of the SNPs rs1048661 and rs3825942 were found to differ significantly between patients and controls (p=0.0056 and p=0.000005). Similar results have been found in most non African populations that have been studied. Genotype frequencies were also compared and the results were not found to be statistically significant. This shows that it is the allele that carries the risk for the disease and not the genotype. Two novel SNPs, found in patients but not in controls, were also reported: g.25722 C>G in exon 4 resulting in D484E was detected in 2 patients and predicted to be benign; and g.28084 T>G in exon 6 resulting in Y559D was detected in 1 patient and predicted to be probably damaging.
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