Expression and significance of lysyl oxidase-like 1 and fibulin-5 in the cardinal ligament tissue of patients with pelvic floor dysfunction

Pelvic organ prolapse （POP） is a disabling disorder in women characterized by a loss of pelvic floor support, leading to the herniation of the uterus into or through the vagina. POP is a complex problem that likely involves multiple mechanisms with limited therapies available, and is associated with defects in connective tissue including elastic fibers. This study was designed to investigate the expression of fibulin-5 and lysyl oxidase-like 1 （LOXL1） in the cardinal ligament in samples taken from the POP group compared to the non-POP group. Specimens were obtained during abdominal hysterectomy from the cardinal ligament of 53 women with POP and 25 age- and par- ity- matched women with non-POP among post-menopausal women with benign gynecologic pathology. Protein expression was evaluated using the immunohistochemical staining method. For statistical analyses, chi-square test and Spearman＇s correlation were used with the statistical package SPSS13.0 system. Our results showed that both fibulin-5 and LOXL1 expressions were decreased in the cardinal ligament in the POP group compared to the non- POP group （P 〈 0.05）. The expression of fibulin-5 and LOXL1 were correlated closely with the stage of POP, ac- companied by stress urinary incontinence and frequency of vaginal delivery （P 〈 0.05）, but had no relationship with post-menopausal state （P 〉 0.05）. The expression of fibulin-5 was positively associated with LOXL1 in POP （P 〈 0.05）. We conclude that changes in fibulin-5 and LOXL1 expression may play a role in the development of POP.

The role of lysyl oxidase-like 1 and fibulin-5 in the development of atherosclerosis and pelvic organ prolapse

Dear Editor： I would like to congratulate Zhou et al.[1] on their study of the correlation between expression of lysyl oxidase-like 1 （LOX-1） and fibulin-5 （F5） in the car- dinal ligament tissue and pelvic organ prolapse （POP）. In their elegant work, they evaluated the levels of LOX-1 and F5 in connective tissue of the cardinal ligament in order to demonstrate signs of elastinopa- thy in women with POP. They stress the concept that several environmental risk factors could cause qualitative and quantitative changes in the connective tissue promoting POP. The above authors conclude that the specific mechanism of LOXL1 and F5 involved in the development of POP is unclear.

Lack of association between lysyl oxidase-like 1 polymorphisms and primary open angle glaucoma: a meta-analysis

AIM:To study the associations between lysyl oxidaselike 1(LOXL1)polymorphisms and primary open angle glaucoma(POAG)remain inconsistent.In this study,we have performed a meta-analysis to investigate the association of LOXL1 polymorphisms with POAG risk.METHODS:Published literature from PubMed and other databases were retrieved.All studies evaluating the association between LOXL1 polymorphisms(rs2165241,rs1048661,rs3825942)and POAG risk were included.Pooled odds ratio(OR)and 95%confidence interval(CI)were calculated using random-or fixed-effects model.RESULTS:Twelve studies were identified as eligible articles,with thirteen(2098 cases and 16 473 controls),thirteen(1795 cases and 2916 controls)and sixteen population cohorts(2456 cases and 2846 controls)for the association of rs2165241,rs1048661 and rs3825942with POAG risk respectively.Overall analyses showed noassociation between each LOXL1 polymorphism and POAG risk,and the negative associations were remained when the subjects were stratified as Caucasian and Asian.The heterozygote of rs2165241 was associated with reduced POAG risk in hospital-based populations(TC vs CC:OR,0.79,95%CI:0.63-0.99),and rs1048661was associated with increased POAG risk in hospitalbased populations in a dominant model(TT vs CC+CT:OR,1.23,95%CI:1.01-1.50);however,these associations were not found in population-based subjects.CONCLUSION:This meta-analysis suggests that LOXL1 polymorphisms are not associated with POAG risk.Given the limited sample size,the associations of LOXL1 polymorphisms with POAG risk in hospital-based populations await further investigation.

LOXL1基因启动子区单核苷酸多态性与维吾尔族剥脱综合征发病的关联性研究

背景 剥脱综合征（XFS）是一种细胞外基质异常聚集的系统性疾病.研究证实,位于赖氨酰氧化酶样1（LOXL1）基因第一外显子区的单核苷酸多态性（SNPs）位点与XFS发病有一定关联,但这些研究在不同种族、国家和地区间结果并不一致.目的 探讨新疆维吾尔族人群中LOXL1基因启动子区SNPs与XFS发病的关联性.方法 采用病例对照研究设计,于2014年1-8月收集新疆地区维吾尔族无亲缘关系的152例XFS患者为XFS组,收集同期民族和性别匹配的228名眼部正常者为对照组.采集所有受检者外周血各5 ml并提取DNA,选取LOXL1基因启动子区rs12914489、rs4886467、rs4558370、rs4461027、rs4886761、rs 16958477共6个SNPs位点,利用PCR-连接酶检测反应（LDR）法对各SNPs位点进行基因分型,采用x2检验分析等位基因频率及基因型频率分布,并计算比值比（OR）值及95％可信区间（CI）.结果 本研究中对照组rs12914489位点偏离Hardy-Weinberg平衡（HWE） （P=0.033）,rs4886467、rs4558370、rs4461027、rs4886761、rs16958477位点均符合HWE.XFS组rs4886467等位基因G和基因型GG频率均低于对照组,差异均有统计学意义（均P=0.00）,为保护因素（OR=0.54,95％CI：0.40 ～0.74,P=0.000;OR=0.51,95％ CI：0.33～0.78,P=0.001）;XFS组rs4558370等位基因G和基因型GG频率均高于对照组,差异均有统计学意义（均P=0.00）,二者是发病危险因素（0R=1.96,95％CI：1.23 ～3.11,P=0.004;OR=2.18,95％CI：1.31 ～3.64,P=0.002）;XFS组rs4461027等位基因C和基因型CC频率均明显高于对照组,差异均有统计学意义（均P=0.00）,二者是发病的危险因素（OR=2.25,95％ CI：1.67 ～3.04,P=0.000;OR=3.06,95％CI：1.89～4.96,P=0.000）;XFS组rs4886761等位基因T和基因型TT频率均高于对照组,差异均有统计学意义（均P=0.00）,二者是发病危险因素（OR=2.44,95％ CI：1.79～3.33,P=0.000;OR=3.02,95％CI：1.63～5.60,P=0.000）;XFS组rs16958477位点等位基因C和基因型CC频率均高于XFS组,差异均有统计学意义（均P=0.00）,二者是发病的危险因素（OR=2.00,95％CI：1.47 ～2.71,P=0.000;OR=2.37,95％CI：1.31～4.27,P=0.004）.结论 新疆维吾尔族人群LOXL1基因启动子区的SNPs与新疆维吾尔族XFS发生存在关联,其中rs4886467位点是发病的保护因素,rs4558370、rs4461027、rs4886761和rs16958477位点是XFS发生的危险因素.

The association of LOXL1 polymorphisms with exfoliation syndrome/glaucoma: Meta-analysis

AIM: To investigate the association of lysyl oxidaselike 1(LOXL1) single nucleotide polymorphisms(SNPs)with exfoliation syndrome(XFS)/exfoliation glaucoma(XFG).METHODS: Published manuscripts from Pub Med and EMBASE were identified until May 2014. Summary odds ratios(ORs) and 95% confidence intervals(CIs) for LOXL1(rs1048661, rs2165241 and rs3825942) polymorphisms and the risk of XFS/XFG were estimated using random-or fixed- effect model.· RESULTS: The three LOXL1 polymorphisms(rs1048661, rs3825942, and rs2165241) were associated with an increased risk for XFS/XFG among Caucasians,with OR 2.19(1.96-2.45), 8.8(6.05-12.79) and 3.41(3.11-3.73), respectively. On the contrast, the rs1048661 and rs2165241, but not rs3825942 polymorphism, have a potential protective effect on XFS/XFG in Asians, with OR0.06(0.02-0.18), 0.15(0.09-0.25), respectively.CONCLUSION: There is strong evidence that LOXL1 polymorphisms are associated with XFS/XFG risk. The strength of risk might be ethnicity-dependent.