Background Exfoliation syndrome (XFS) is a systemic disease with abnormal accumulation of extracellular matrix.Researches showed that the single nucleotide polymorphisms (SNPs) of lysyl oxidase-like 1 (LOXL1) gene is associated with the pathogenesis of XFS in global population.However,the results are varied among different ethnicity and regions.Objective This study aimed to assess the association between LOXL1 gene polymorphisms and XFS in Uygur population.Methods One-hundred and fifty-two Uygur XFS patients without relativeness were enrolled from January to August in 2014,and 228 ethnicity-and gender-matched normal controls were recruited at the same period from the same region.Each individual underwent comprehensive eye examinations and 5 ml peripheral blood was collected.Genomic DNA was extracted from peripheral blood.PCR-ligase detection response (LDR) was used to determine the allele and genotype frequencies of the six SNPs rs12914489,rs4886467,rs4558370,rs4461027,rs4886761 and rs16958477 in the promoter region of LOXL1 gene.The distribution frequency between the patients and normal controls was compared by x2 test.Logistic regression analysis was used for age adjustment.This study was approved by Ethic Committe of Xinjiang Medical University,and informed consent was obtained from the subjects.Results rs12914489 site in the normal control group diverged from Hardy-Weinberg equilibrium (HWE) (P =0.033),and the rs4886467,rs4558370,rs4461027,rs4886761 and rs16958477 sites followed HWE.The frequencies of G allele and GG genotype of rs4886467 in the XFS group were lower than those in the control group (both at P =0.00) and were protective factors of XFS (OR =0.54,95 ％ CI:0.40-0.74,P =0.000;OR=0.51,95％ CI:0.33-0.78,P=0.001);the frequencies of T allele and TT genotype of rs4558370 in the XFS group were significantly higher than those in the control group (both at P=0.00) and were the risk factors of XFS (OR=1.96,95％ CI:1.23-3.11,P =0.004;OR =2.18,95％ CI:1.31-3.64,P =0.002);the frequencies of C allele and CC genotype of rs4461027 in the XFS group were significantly higher than those in the control group (both at P=0.00) and were the risk factors of XFS (OR=2.25,95％ CI:1.67-3.04,P=0.000;OR=3.06,95％ CI:1.89-4.96,P=0.000);the frequencies of T allele and TT genotype of rs4886761 in the XFS group were significantly higher than those in the control group (both at P=0.00) and were the risk factors of XFS (OR=2.44,95％ CI:1.79-3.33,P =0.000;OR =3.02,95％ CI:1.63-5.60,P =0.000);the frequencies of C allele and CC genotype of rs16958477 in the XFS group were significantly higher than those in the control group (both at P=0.00) and were the risk factors of XFS (OR =2.00,95 ％ CI:1.47-2.71,P =0.000;OR =2.37,95 ％ CI:1.31-4.27,P =0.004).Conclusions The SNPs of promoter region of LOXL1 gene are associated with hereditary susceptibility of XFS individually in Uygur population.The SNPs of rs4886467 locus are protective factor,while the SNPs of rs4558370,rs4461027,rs4886761 and rs16958477 locus are risk factors for pathogenesis of XFS.

Objective:To investigate the effect of knocking down the lysyl oxidase-like protein 1 ( LOXL1) gene on the expression and aggregation of elastin in the human lens epithelial cells (HLECs), as well as its impact on the proliferation activity and migration ability of HLECs. Methods:The human lens epithelial cell line HLE-B3 was cultured in vitro and divided into shLOXL1-1 group, shLOXL1-2 group, shLOXL1-3 group, and normal control group.The shLOXL1-1 group, shLOXL1-2 group, and shLOXL1-3 group cells were subjected to LOXL1 gene knockdown intervention using different sequences of lentiviral transfection methods, while the normal control group was subjected to meaningless sequence lentiviral transfection intervention.The relative expression level of LOXL1 mRNA in different groups was detected by real-time fluorescence quantitative PCR.The fluorescence intensity of elastin in HLE-B3 was determined by immunofluorescence.The expression of elastin in HLE-B3 was detected by Western blot.The content and aggregation degree of elastin in HLE-B3 was detected by electron microscopy scanning.The migration rate of HLE-B3 was detected by cell scratch assay.The proliferation activity of HLE-B3 was detected using the cell counting kit 8. Results:After knocking down the LOXL1 gene, the relative expression levels of LOXL1 mRNA were lower in the shLOXL1-1, shLOXL1-2, and shLOXL1-3 groups than those in the normal control group, and the differences were statistically significant (all at P<0.001).The shLOXL1-3 group had the best knockdown effect, so the shLOXL1-3 group was selected for subsequent experiments and compared with the normal control group.After immunofluorescence staining, stable expression of elastin was observed in HLE-B3 cells.The average fluorescence intensity of elastin in the shLOXL1-3 group was 56.96±5.56, significantly lower than 80.52±4.78 in the normal control group ( t=5.572, P<0.001).The relative expression level of elastin in the shLOXL1-3 group was 0.807±0.002, significantly lower than 1.185±0.064 in the normal control group ( t=5.802, P<0.01).Under the electron microscope, the elastin density in the shLOXL1-3 group was lower than that in the normal control group, but its morphology, size, and aggregation degree did not show significant changes.At 24 and 48 hours after transfection, the relative migration rates of shLOXL1-3 group cells were 0.292±0.041 and 0.439±0.032, which were lower than 0.463±0.017 and 0.719±0.007 of normal control group, respectively, and the differences were statistically significant ( t=8.178, 2.611; both at P<0.05).After 24, 48, 72, and 96 hours of cultivation, the cell viability values of shLOXL1-3 group were lower than those of normal control group, and the differences were statistically significant ( t=2.555, 2.704, 6.695, 7.266; all at P<0.05). Conclusions:Knocking down the LOXL1 gene in HLECs can cause a significant decrease in the expression level of elastin in the cells, as well as decreases in cell migration ability and proliferation activity.