Coding variants in the lysyl oxidase-like 1 (LOXL1) gene are strongly associated with XFS in all studied populations, but a functional role for these variants has not been established.
Interestingly, lamina cribrosa specimens of early and late XFS stages without and with glaucoma revealed a selective downregulation of LOXL1 and elastic fiber components on the mRNA and protein level, which was associated with pronounced ultrastructural alterations of the laminar elastic fiber network in XFS eyes.
The discovery in 2007 of nonsynonymous single nucleotide polymorphisms in the LOXL1 (lysyl oxidase-like 1) gene are expected to make a major impact not only in understanding exfoliation syndrome, but in leading to new avenues of therapy.
Sequencing of the LOXL1 gene in XFG participants identified a total of 212 SNPs, of which 49 exhibited allelic frequencies with significant differences between cases and controls, and 66 were not previously described.
Our findings represent the first genetic locus outside of LOXL1 surpassing genome-wide significance for XFS and provide insight into the biology and pathogenesis of the disease.
Our findings represent the first genetic locus outside of LOXL1 surpassing genome-wide significance for XFS and provide insight into the biology and pathogenesis of the disease.
Our findings represent the first genetic locus outside of LOXL1 surpassing genome-wide significance for XFS and provide insight into the biology and pathogenesis of the disease.
A role for microfibrils in glaucoma is suggested by identification of risk alleles in LOXL1 for exfoliation glaucoma and mutations in LTBP2 for primary congenital glaucoma, both of which are microfibril-associated genes.
Moreover, further analyses revealed a unique haplotype structure only from the combination of TBC1D21 and LOXL1 variants showing a high XFS/XFG susceptibility specific for the Asian population.
A probable intragenic epistasis effect was assessed by comparing the frequencies of the rs41435250 alleles among a subset of 51 patients with XFS/XFG without the high-risk TT genotype at LOXL1 intronic rs2165241 and the control group.
Our results also confirm in a Turkish population the findings of previous reports describing the association between LOXL1 polymorphisms and XFS/XFG but not with POAG.
The purpose of this study was to report the results of the first association study between LOXL1 polymorphisms and XFS and/or XFG in a Latin American population.
The regions of the LOXL1 gene associated with pseudoexfoliation glaucoma, encompassing the three common SNPs, (rs1048661, rs3825942 and rs2165241), were sequenced in a Saudi Arabian dataset consisting of 96 POAG cases and 101 healthy controls.