Lysyl Oxidase-Like 1 Polymorphisms in Children of Patients With Exfoliation Syndrome (XFS)

Abstract

Purpose: : Single nucleotide polymorphisms (SNPs) in the LOXL1 gene have been implicated as the principal genetic risk factor for XFS. We examined LOXL1 polymorphisms in asymptomatic children of patients previously diagnosed with XFS.

Methods: : We recruited 30 asymptomatic adult children (12M, 28F18F) HOW DOES 12 AND 28 ADD UP TO 30? of 21 patients (4M, 17F) diagnosed with XFS with or without glaucoma. LOXL1 gene polymorphisms [rs1048661 ((R141L), rs3825942 (G153D), and rs2165241]) were genotyped in all 51 subjects (parents and children) by direct sequencing. Association studies between two subject groups were carried out with kappa inter-rate agreement test.

Results: : Parent-child genotypic comparisons of R141L (0.667, Κ=.40) and G153D (0.719, Κ=.45) were significant for strong hereditary correlations and rs2165241 (0.387 Κ=.04) was not. 66.7% and 71.2% of the offspring matched the genotype of their parents for R141L and G153D SNPs, respectively. Only 38.7% of the children matched genotypically from their parents on the rs2165241 allele. In view of this observation, clinically significant correlations were established in both R141L and G153D between parent and offspring. The allelic frequencies for R141L (G/G) high-risk genotype were 0.667 for children and 0.714 for parents. The allelic frequencies for G153D (G/G) high-risk genotype were 0.850 and 0.733 for parents and children, respectively. 29.0% of children and 52.3% of parents presented with the rs2165241 (T/T) high risk genotype.

Conclusions: : Although these children are asymptomatic othe children genotyped do not have clinically evidentf XFS, strong hereditary correlations between the LOXL1 gene and parental clinical diagnosis of XFS present a strong case for careful ophthalmic monitoring. LOXL1 genotyping can be used to detect the presence of LOXL1 SNPs as a significant risk factor for exfoliation XFSsyndrome.

Keywords: genetics • gene/expression • clinical (human) or epidemiologic studies: risk factor assessment