382例溃疡性结肠炎患者维生素D受体基因多态性及单倍型分析
382례궤양성결장염환자유생소D수체기인다태성급단배형분석
Analysis on the genetic polymorphisms and haplotypes of vitamin D receptor in three hundred and eighty-two patients with ulcerative colitis
  • 万方数据
    中华消化杂志 중화소화잡지
    Chinese Journal of Digestion
    2014年 7期 458-462 ,共5页

    夏盛隆%俞俐琴%裴继华%胡定元%邵晓晓%金捷%林秀清%李士林%蒋益

    하성륭%유리금%배계화%호정원%소효효%금첩%림수청%리사림%장익

    结肠炎,溃疡性%受体,骨化三醇%基因多态性 結腸炎,潰瘍性%受體,骨化三醇%基因多態性
    결장염,궤양성%수체,골화삼순%기인다태성
    Colitis,ulcerative%Receptors,calcitriol%Gene polymorphism
    目的 探讨浙江汉族人群维生素D受体(VDR) FokⅠ、BsmⅠ、ApaⅠ、TaqⅠ及其构成的单倍型与UC的关系.方法 收集2004年1月至2012年9月的UC患者382例.同期收集489名年龄、性别匹配的健康体检者作为对照.取研究对象空腹外周静脉血2mL,提取全基因组DNA.采用微测序技术,经多重PCR扩增、PCR产物纯化、延伸反应和二次纯化、毛细管电泳检测基因型,测定VDR基因多态性.用卡方检验分析对照组VDR FokⅠ、BsmⅠ、ApaⅠ、TaqⅠ的基因型分布是否符合HardyWeinberg平衡定律.校正年龄、性别、吸烟因素后,采用非条件Logistic回归分析法比较UC组和对照组间VDR FokⅠ、BsmⅠ、ApaⅠ、TaqⅠ的等位基因和基因型频率差异,以及其对UC患者临床病理特征的影响.用Haploview 4.2软件进行连锁不平衡和单倍型分析.结果 对照组中VDRFokⅠ、BsmⅠ、ApaⅠ、TaqⅠ的基因型分布均符合Hardy-Weinberg平衡定律(P均＞0.05).校正年龄、性别和吸烟因素后,非条件Logistic回归分析显示,UC组和对照组VDR FokⅠ、BsmⅠ、ApaⅠ、TaqⅠ的等位基因和基因型频率差异均无统计学意义(P均＞0.05).轻度和中度UC患者VDRFokⅠ位点的突变等位基因C和TC+CC基因型的频率[54.14％(353/652)和81.60％(266/326)]均高于重度UC患者[39.29％(44/112)和57.14％(32/56),OR=1.825和3.322,95％CI分别为1.212～2.747和1.828～6.061,P均＜0.01].DR BsmⅠ、ApaⅠ和TaqⅠ与UC疾病严重程度无关(P均＞0.05).UC远端结肠炎和广泛结肠炎患者VDR FokⅠ、BsmⅠ、ApaⅠ、TaqⅠ的突变等位基因频率和基因型频率差异均无统计学意义(P均＞0.05).VDR BsmⅠ、ApaⅠ和TaqⅠ之间存在连锁不平衡;BsmⅠ与ApaⅠ的连锁不平衡系数(D ’)=0.982,相关系数(r2)=0.156;ApaⅠ与TaqⅠ的D'=0.929,r2=0.141;BsmⅠ与TaqⅠ的D'=0.826,r2=0.675.在8种单倍型(GAC、ACC、GCC、AAT、ACT、GCT、GAT、AAC)中,仅UC组AAC单倍型的频率[3.80％ (29/764)]低于对照组[5.93％(58/978)],差异有统计学意义(OR=0.631,95％CI 0.394～1.013,P=0.039).结论 VDR FokⅠ基因突变可能影响UC患者的疾病严重程度.携带BsmⅠ、ApaⅠ、TaqⅠ构成的AAC单倍型的个体罹患UC的风险可能较低.
    목적 탐토절강한족인군유생소D수체(VDR) FokⅠ、BsmⅠ、ApaⅠ、TaqⅠ급기구성적단배형여UC적관계.방법 수집2004년1월지2012년9월적UC환자382례.동기수집489명년령、성별필배적건강체검자작위대조.취연구대상공복외주정맥혈2mL,제취전기인조DNA.채용미측서기술,경다중PCR확증、PCR산물순화、연신반응화이차순화、모세관전영검측기인형,측정VDR기인다태성.용잡방검험분석대조조VDR FokⅠ、BsmⅠ、ApaⅠ、TaqⅠ적기인형분포시부부합HardyWeinberg평형정률.교정년령、성별、흡연인소후,채용비조건Logistic회귀분석법비교UC조화대조조간VDR FokⅠ、BsmⅠ、ApaⅠ、TaqⅠ적등위기인화기인형빈솔차이,이급기대UC환자림상병리특정적영향.용Haploview 4.2연건진행련쇄불평형화단배형분석.결과 대조조중VDRFokⅠ、BsmⅠ、ApaⅠ、TaqⅠ적기인형분포균부합Hardy-Weinberg평형정률(P균＞0.05).교정년령、성별화흡연인소후,비조건Logistic회귀분석현시,UC조화대조조VDR FokⅠ、BsmⅠ、ApaⅠ、TaqⅠ적등위기인화기인형빈솔차이균무통계학의의(P균＞0.05).경도화중도UC환자VDRFokⅠ위점적돌변등위기인C화TC+CC기인형적빈솔[54.14％(353/652)화81.60％(266/326)]균고우중도UC환자[39.29％(44/112)화57.14％(32/56),OR=1.825화3.322,95％CI분별위1.212～2.747화1.828～6.061,P균＜0.01].DR BsmⅠ、ApaⅠ화TaqⅠ여UC질병엄중정도무관(P균＞0.05).UC원단결장염화엄범결장염환자VDR FokⅠ、BsmⅠ、ApaⅠ、TaqⅠ적돌변등위기인빈솔화기인형빈솔차이균무통계학의의(P균＞0.05).VDR BsmⅠ、ApaⅠ화TaqⅠ지간존재련쇄불평형;BsmⅠ여ApaⅠ적련쇄불평형계수(D ’)=0.982,상관계수(r2)=0.156;ApaⅠ여TaqⅠ적D'=0.929,r2=0.141;BsmⅠ여TaqⅠ적D'=0.826,r2=0.675.재8충단배형(GAC、ACC、GCC、AAT、ACT、GCT、GAT、AAC)중,부UC조AAC단배형적빈솔[3.80％ (29/764)]저우대조조[5.93％(58/978)],차이유통계학의의(OR=0.631,95％CI 0.394～1.013,P=0.039).결론 VDR FokⅠ기인돌변가능영향UC환자적질병엄중정도.휴대BsmⅠ、ApaⅠ、TaqⅠ구성적AAC단배형적개체리환UC적풍험가능교저.
    Objective To investigate the relationship between polymorphisms and haplotypes of vitamin D receptor (VDR) genes FokⅠ,BsmⅠ,ApaⅠ,TaqⅠ and ulcerative colitis (UC) in Han population of Zhejiang province.Methods From January 2004 to September 2012,382 patients with UC were collected and 489 age and gender matched healthy individuals were collected at the same period as controls.Two milliliter fasting peripheral blood of subjects was obtained for whole-genome DNA isolation.Microsequencing technology was applied.Polymnorphisms of VDR were determined through multiplex polymerase chain reaction (PCR) amplification,PCR products purification,extension,second purification and capillary electrophoresis genotype.Whether the distribution of VDR FokⅠ,BsmⅠ,ApaⅠ,Taq Ⅰ genotype of control group met Hardy-Weinberg equilibrium was analyzed by chi-square test.After age,gender and smoking factors adjusted,the differences of VDR FokⅠ,BsmⅠ,ApaⅠ,TaqⅠ allele and genotype frequencies between UC group and control group were analyzed by non-conditional Logistic regression analysis,and their effects on clinic-pathological features of patients with UC were also analyzed.Linkage disequilibrium and haplotype analysis was made by Haploview 4.2 software.Results The distributions of VDR FokⅠ,Bsm],ApaⅠ,TaqⅠ genotype met Hardy-Weinberg equilibrium (all P＞0.05).After age,gender and smoking factors adjusted,the results of non conditional Logistic regression analysis indicated that there were no significant differences in VDR FokⅠ,BsmⅠ,ApaⅠ,TaqⅠ allele and genotype frequencies between UC group and control group (all P＞0.05).However,the frequencies of mutant allele (C) and genotype (TC+CC) in VDR FokⅠ of patients with mild and moderate UC (54.14％,353/652 ; 81.60％,266/326) were significantly higher than those of patients with severe UC (39.29％,44/112; 57.14％,32/56; OR=1.825 and 3.322,95％CI 1.212 to 2.747 and 1.828 to 6.061,both P＜0.01).There was no correlation between VDR BsmⅠ,ApaⅠ,TaqⅠ and severity of UC (all P＞0.05).There were no significant differences in VDR FokⅠ,BsmⅠ,ApaⅠ,TaqⅠ allele and genotype frequencies between UC patients with distal colitis and extensive colitis (all P＞0.05).There were linkage disequilibrium in VDR BsmⅠ,ApaⅠ and TaqⅠ.Linkage disequilibrium coefficient (D') between BsmⅠ and ApaⅠ was 0.982 and the correlation coefficient (r2) was 0.156; D' between ApaⅠ and TaqⅠ was 0.929 and r2 was 0.141; D' between BsmⅠ and TaqⅠ was 0.826 and r2 was 0.675.Among eight haplotypes (GAC,ACC,GCC,AAT,ACT,GCT,GAT and AAC),the frequency of AAC haplotype of UC group (3.80％,29/764)was lower than that of control group (5.93％,58/978) and the difference was statistically significant (OR=0.631,95％CI 0.394-1.013,P=0.039).Conclusions The genetic mutation of VDR FokⅠ may influence severity of patients with UC.The risk of developing UC is low in the individuals carrying AAC haplotype of VDR BsmⅠ,ApaⅠ,TaqⅠ suffering UC.
    원문보기 원문다운로드 사이트로이동
저자의 최근 논문