先天性髋脱位与同源盒基因传递不平衡研究(英文)  

Transmission disequilibrium between congenital dislocation of the hip and homeobox-containing genes

作　　者：麻宏伟[1] 卢瑶[1] 姜俊[1] 王岳平[1] 李祁伟[2] 王旸[1] 吉士俊[2] 

机构地区：[1]中国医科大学附属第二医院发育儿科,遗传研究室,辽宁省沈阳市110004 [2]中国医科大学附属第二医院小儿外科,辽宁省沈阳市110004

出　　处：《中国临床康复》2005年第6期190-192,i008,共4页Chinese Journal of Clinical Rehabilitation

基　　金：国家自然科学基金项目资助(39970762);辽宁省自然科学基金项目资助(972248)~~

摘　　要：背景:目前研究表明遗传因素在先天性髋脱位(congenitaldislocationofthehip,CDH)的发病中起重要作用。但迄今为止,从基因水平研究其发生机制报道较少。同源盒(homeobox,HOX)基因是胚胎发育和脊椎动物肢体发育的重要调控基因,因此推测HOX基因可能与CDH的发病有关。目的:探讨CDH与HOX基因是否存在相关性。设计:核心家系内对照关联研究。单位:一所大学医院的发育儿科、遗传研究室及小儿外科。对象:101个CDH核心家系303名成员均为中国医科大学第二临床学院小儿骨科病房1999-12/2001-01间全部住院CDH患者及其父母,所有患者均有典型的临床表现,经X射线检查及手术确诊。方法:在胚胎肢体发育调控相关基因-HOX基因A簇、B簇、C簇和D簇所在的染色体区域7P14-15,17q21,12q13和2q31内选择4个微卫星DNA标记D7S1808,D17S1820,D12S1686和Hox4EP,应用聚合酶链反应及变性聚丙烯酰胺凝胶电泳技术,对101个先天性髋脱位核心家系的303名成员进行基因型分析,并进行传递不平衡检验(TDT)。主要观察指标:确定101个CDH核心家系303名成员4个微卫星DNA标记D7S1808,D17S1820,D12S1686和Hox4EP的基因型,对父母传递和不传递给患者的等位基因进行传递不平衡检验。结果:在D12S1686多态性标记位点上共检测到16个等位基因,TDT分析显示。BACKGROUND:Research shows that genetic factors are an important component of the congenital dislocation of the hip(CDH). However,no susceptibility genes have been identified by now. The homebox containing(HOX) genes that regulate the embryogenesis and vertebrate limb development may play a role in the pathogenesis of CDH. OBJECTIVE:To investigate whether a correlation exists between CDH and the Hox genes. DESIGN:Controlled study associated with family. SETTING:Department of aevelopmental pediatrics,genetic laboratory,department of pediatric orthopaedics in an affiliated hospital of a university. PARTICIPANTS:All the 101 CDH patients and their parents (altogether 303 members) were the in patients from the Department of Pediatric Orthopaedics of the Second Clinical College of China Medical University from December 1999 to January 2001.All the patients presented typical clinical manifestations and were diagnosed by X rays and operations for confirmation. METHODS:Four microsatellite markers D7S1808,D17S1820, D12S1686 and Hox4EP were selected in the chromosome regions of 7p14- 15,17q21,12q13 and 2q31 where Hox A,Hox B,Hox C and Hox D genes which regulate the embryonic limb development reside respectively.Genotypes of 303 members in 101 CDH families were analyzed by the techniques of polymerase chain reaction(PCR) and denaturing polyacrylamide gel electrophoresis.Then transmission disequilibrium test(TDT) was performed to analyze the data of genotypes. MAIN OUTCOME MEASURES:The genotypes of four microsatellite markers D7S1808,D17S1820,D12S1686 and Hox4EP in every CDH family including one child and parents;transmission disequilibrium test between transmission alleles and non transmission alleles. RESULTS:Transmission disequilibrium was found between CDH and allele 7 of D7S1808( χ 2=6.045, P=0.014) among a total of 10 alleles detected, between CDH and allele 4 of D17S1820(χ 2=6.025, P=0.014) among a total of 12 alleles detected, between CDH and allele 4 of Hox4Ep( χ 2=6.461, P=0.011) among a total of 16 allele

关 键 词：先天性髋脱位 传递不平衡检验 110X基因 

分 类 号：R683[医药卫生—骨科学]