中国宁夏地区年龄相关性黄斑变性患者的补体基因和ARMS2/HTRA1基因多态性分析  

Polymorphisms of complement genes and ARMS2/HTRAI in patients with age-related macular degeneration in Ningxia, China

作　　者：李武靓 庄文娟 李慧平 刘雅妮 哈少平 盛迅伦 

机构地区：[1]宁夏医科大学临床医学系,银川750004 [2]宁夏人民医院宁夏眼科医院,银川750011

出　　处：《中华实验眼科杂志》2015年第2期149-154,共6页Chinese Journal Of Experimental Ophthalmology

基　　金：国家重点基础研究发展计划项目（2011CB510200）

摘　　要：背景 年龄相关性黄斑变性（AMD）是导致全球老年人中心视力不可逆丧失的主要原因,且发病率逐年上升,但其发病机制一直是研究的热点. 目的 探讨补体因子H（CFH）、补体因子B（CFB）、年龄相关性黄斑变性易感基因2（ARMS2）/高温需求因子A1（HTRA1）基因多态性与宁夏地区人群AMD的相关性.方法 采用病例对照关联分析的方法,收集宁夏地区无亲缘关系的AMD患者150例为AMD组,民族、性别与之相匹配的拟行白内障手术者（排除其他眼部疾患）145例为对照组,采集所有受检者外周血5～10 ml,并提取DNA.选取CFH、CFB、ARMS2和HTRA1基因上的8个单核苷酸多态性（SNPs）位点,分别为位于CFH基因上的rs551397、rs800292、rs12124794、rs10737680、rs1410996,CFB基因上的rs641153,ARMS2基因上的rs10490924及HTRA1基因上的rs11200638,运用MassARRAY实验平台提供的MALDI-TOF分析软件对这些位点进行基因分型.采用χ^2检验及非条件Logistic回归模型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）,同时对多重比较进行Bonferroni检验校正,P＜0.006为差异有统计学意义.此外,运用Haploview软件分析各连锁不平衡区块以及基于连锁不平衡的单体型. 结果 所有SNPs位点基因型均符合Hardy-Weinberg平衡（HWE）.AMD组与对照组间共有7个SNPs位点基因型频率及等位基因频率上差异有统计学意义（P＜0.05）,但经过Bonferroni校正后,只有rs10737680、rs1410996、rs10490924、rs11200638基因型频率及等位基因频率在AMD组与对照组间差异均有统计学意义[P=0.003,P=0.003,P＜0.001,P＜0.001（均OR=1.000）];而rs800292（P=0.006,OR=1.643,95％CI：1.155 ～2.336）及rs641153（P=0.002,OR=0.273,95％ CI：0.120 ～0.620）2个位点仅在等位基因频率差异有统计学意义.此外,通过Haploview软件分析单体型发现,rs551397和rs800292位于同一个连锁不平衡区域,其单体型GC和AT�Background Age-related macular degeneration （AMD） is the main cause of irreversible loss of central vision in old population.The incidence of AMD is increasing year by year,but the mechanism is not clearly understood.Objective This study was to investigate the association between genetic variants and the risk of AMD in Ningxia population.Methods This study was approved by Ethic Committee of Ningxia People＇s Hospital and complied with the Helsinki Declaration.Written informed consent was obtained from each subject.One hundred and fifty patients with AMD and 145 ethnicity-and gender-matched controls were recruited in Ningxia Eye Hospital from January 2012 to March 2013.All individuals underwent comprehensive eye examinations and genomic DNA was prepared from peripheral blood.The single nucleotide polymorphisms （SNPs） of 8 susceptibility loci in four candidate genes,including complement factor H （CFH）,complement factor B （CFB）,age-related maculopathy susceptibility 2 （ARMS2） and high temperature required factor A1 （HTRA1）,were genotyped with Mass Array and MALDI-TOF technique by Sequenom platform.The distribution of genotype was tested for Hardy-Weinberge equilibrium （HWE）.The differences of genotype distribution of allele and haplotype frequencies were compared between patients and controls using chi-squared test and the P value was significant at 〈 0.006 level after correction of age,and the relationship of genotype distribution with AMD was evaluated by Logistic regression analysis.Measures of linkage disequilibrium （LD） was carried out by Haploview.Results All the genetypes met HWE.Seven SNPs were found to be different in the genotypic distributions and allele frequencies between patients and normal controls （all at P〈 0.05）,however,after Bonferroni correction,the differences of only four SNPs were significant between the patients and controls in the genotype and allele distributions,including the SNPs of rs10737680 and rs1410996 in CFH gene,the SNP of rs10490924 in ARMS

关 键 词：老年 补体因子/基因学 基因频率 黄斑变性/基因学 基因多态性 疾病基因易感性 

分 类 号：R774.5[医药卫生—眼科]