中华实验眼科杂志
中華實驗眼科雜誌
중화실험안과잡지
CHINESE JOURNAL OF EXPERIMENTAL OPHTHALMOLOGY
2015年
2期
149-154
,共6页
李武靓%庄文娟%李慧平%刘雅妮%哈少平%盛迅伦
李武靚%莊文娟%李慧平%劉雅妮%哈少平%盛迅倫
리무정%장문연%리혜평%류아니%합소평%성신륜
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
老年%補體因子/基因學%基因頻率%黃斑變性/基因學%基因多態性%疾病基因易感性
노년%보체인자/기인학%기인빈솔%황반변성/기인학%기인다태성%질병기인역감성
Aged%Complement factor/genetics%Gene frequency%Macular degeneration/genetics%Polymorphisms,genetic%Genetic predisposition to diseases
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x2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经过50 000次的置换检验后,在AMD组和对照组间差异均有统计学意义(P=0.010、0.010),而位于另一个连锁不平衡区域的rs12124794、rs10737680和rs1410996位点的单体型AAC、TCT、TCT频率在AMD组和对照组间的差异亦均有统计学意义(P=0.001、0.041、0.033).rs641153位点等位基因T为AMD的保护因素(P=0.002,OR=0.273,95％CI:0.120 ～0.620). 结论 CFH基因rs10737680及rs1410996位点、ARMS2基因rs10490924位点和HTRA1基因rs11200638位点的SNPs与宁夏地区人群AMD的发生存在相关性,是AMD发生的危险因素.
揹景 年齡相關性黃斑變性(AMD)是導緻全毬老年人中心視力不可逆喪失的主要原因,且髮病率逐年上升,但其髮病機製一直是研究的熱點. 目的 探討補體因子H(CFH)、補體因子B(CFB)、年齡相關性黃斑變性易感基因2(ARMS2)/高溫需求因子A1(HTRA1)基因多態性與寧夏地區人群AMD的相關性.方法 採用病例對照關聯分析的方法,收集寧夏地區無親緣關繫的AMD患者150例為AMD組,民族、性彆與之相匹配的擬行白內障手術者(排除其他眼部疾患)145例為對照組,採集所有受檢者外週血5～10 ml,併提取DNA.選取CFH、CFB、ARMS2和HTRA1基因上的8箇單覈苷痠多態性(SNPs)位點,分彆為位于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,運用MassARRAY實驗平檯提供的MALDI-TOF分析軟件對這些位點進行基因分型.採用x2檢驗及非條件Logistic迴歸模型分析等位基因頻率及基因型頻率分佈,併計算比值比(OR)值及95％可信區間(CI),同時對多重比較進行Bonferroni檢驗校正,P＜0.006為差異有統計學意義.此外,運用Haploview軟件分析各連鎖不平衡區塊以及基于連鎖不平衡的單體型. 結果 所有SNPs位點基因型均符閤Hardy-Weinberg平衡(HWE).AMD組與對照組間共有7箇SNPs位點基因型頻率及等位基因頻率上差異有統計學意義(P＜0.05),但經過Bonferroni校正後,隻有rs10737680、rs1410996、rs10490924、rs11200638基因型頻率及等位基因頻率在AMD組與對照組間差異均有統計學意義[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箇位點僅在等位基因頻率差異有統計學意義.此外,通過Haploview軟件分析單體型髮現,rs551397和rs800292位于同一箇連鎖不平衡區域,其單體型GC和AT經過50 000次的置換檢驗後,在AMD組和對照組間差異均有統計學意義(P=0.010、0.010),而位于另一箇連鎖不平衡區域的rs12124794、rs10737680和rs1410996位點的單體型AAC、TCT、TCT頻率在AMD組和對照組間的差異亦均有統計學意義(P=0.001、0.041、0.033).rs641153位點等位基因T為AMD的保護因素(P=0.002,OR=0.273,95％CI:0.120 ～0.620). 結論 CFH基因rs10737680及rs1410996位點、ARMS2基因rs10490924位點和HTRA1基因rs11200638位點的SNPs與寧夏地區人群AMD的髮生存在相關性,是AMD髮生的危險因素.
배경 년령상관성황반변성(AMD)시도치전구노년인중심시력불가역상실적주요원인,차발병솔축년상승,단기발병궤제일직시연구적열점. 목적 탐토보체인자H(CFH)、보체인자B(CFB)、년령상관성황반변성역감기인2(ARMS2)/고온수구인자A1(HTRA1)기인다태성여저하지구인군AMD적상관성.방법 채용병례대조관련분석적방법,수집저하지구무친연관계적AMD환자150례위AMD조,민족、성별여지상필배적의행백내장수술자(배제기타안부질환)145례위대조조,채집소유수검자외주혈5～10 ml,병제취DNA.선취CFH、CFB、ARMS2화HTRA1기인상적8개단핵감산다태성(SNPs)위점,분별위위우CFH기인상적rs551397、rs800292、rs12124794、rs10737680、rs1410996,CFB기인상적rs641153,ARMS2기인상적rs10490924급HTRA1기인상적rs11200638,운용MassARRAY실험평태제공적MALDI-TOF분석연건대저사위점진행기인분형.채용x2검험급비조건Logistic회귀모형분석등위기인빈솔급기인형빈솔분포,병계산비치비(OR)치급95％가신구간(CI),동시대다중비교진행Bonferroni검험교정,P＜0.006위차이유통계학의의.차외,운용Haploview연건분석각련쇄불평형구괴이급기우련쇄불평형적단체형. 결과 소유SNPs위점기인형균부합Hardy-Weinberg평형(HWE).AMD조여대조조간공유7개SNPs위점기인형빈솔급등위기인빈솔상차이유통계학의의(P＜0.05),단경과Bonferroni교정후,지유rs10737680、rs1410996、rs10490924、rs11200638기인형빈솔급등위기인빈솔재AMD조여대조조간차이균유통계학의의[P=0.003,P=0.003,P＜0.001,P＜0.001(균OR=1.000)];이rs800292(P=0.006,OR=1.643,95％CI:1.155 ～2.336)급rs641153(P=0.002,OR=0.273,95％ CI:0.120 ～0.620)2개위점부재등위기인빈솔차이유통계학의의.차외,통과Haploview연건분석단체형발현,rs551397화rs800292위우동일개련쇄불평형구역,기단체형GC화AT경과50 000차적치환검험후,재AMD조화대조조간차이균유통계학의의(P=0.010、0.010),이위우령일개련쇄불평형구역적rs12124794、rs10737680화rs1410996위점적단체형AAC、TCT、TCT빈솔재AMD조화대조조간적차이역균유통계학의의(P=0.001、0.041、0.033).rs641153위점등위기인T위AMD적보호인소(P=0.002,OR=0.273,95％CI:0.120 ～0.620). 결론 CFH기인rs10737680급rs1410996위점、ARMS2기인rs10490924위점화HTRA1기인rs11200638위점적SNPs여저하지구인군AMD적발생존재상관성,시AMD발생적위험인소.
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 ARMS2 gene and SNP of rs11200638 in HTRA1 gene.The allele distributions of rs800292 (Pallele =0.006,OR =1.643,95 ％ CI:1.155-2.336) in CFH and rs641153 (Pallele =0.002,OR =0.273,95 ％ CI:0.120-0.620) in CFB were significantly associated with AMD.In addition,five SNPs in CFH gene were consisted of two blocks after analysis by Haploview.In addition,five SNPs in CFH were consisted of two blocks after analysis by Haploview.The first one SNPs (including rs551397 and rs800292) and another one SNPs (including rs12124794,rs10737680) and rs1410996 were in strong linkage disequilibrium (D'=1.00).After 50 000 permutations,the GC and AT haplotypes of the first block and the AAC,TCT and ACT haplotypes in the second block were significantly different between AMD patients and controls (P =0.010,0.010,0.001,0.041 and 0.033,respectively).The allel T of rs641153 was a protective factor of AMD (P=0.002,OR =0.273,95％ CI:0.120-0.620).Conclusions The SNPs rs10737680 and rs1410996 in CFH,rs10490924 of ARMS2 gene and rs11200638 of HTRA1 gene are associated with AMD in Ningxia population.
