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  

Association between single nucleotide polymorphisms at LOXL1 promoter and Uygur patients with exfoliation syndrome

作　　者：郭梦颖[1] 杨梦婷[1] 玛依努[1] 张明媚[1] 陈雪艺[1] 

机构地区：[1]新疆医科大学第一附属医院眼科,乌鲁木齐830054

出　　处：《中华实验眼科杂志》2015年第8期733-738,共6页Chinese Journal Of Experimental Ophthalmology

基　　金：国家自然科学基金项目（81360153）

摘　　要：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�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 =0.0

关 键 词：剥脱综合征 赖氨酰氧化酶样1基因 启动子区 多态性 单核苷酸 疾病基因易感性 

分 类 号：R771.3[医药卫生—眼科]