云南基诺族及汉族特发性全面强直-阵挛性癫痫与CLCN2基因的相关性  

Dependability search of human CLC-2 gene associated with idiopathic generalized tonic-clonic seizures in Jinuo people and Han people from Yunnan province

作　　者：梁丽君[1] 常履华[1] 任惠[1] 俞志鹏[1] 宿兵[2] 

机构地区：[1]昆明医学院第一附属医院神经内科 [2]中国科学院昆明动物研究所

出　　处：《中华神经科杂志》2007年第11期741-745,共5页Chinese Journal of Neurology

基　　金：国家自然科学基金(30560043)

摘　　要：目的研究氯离子通道 CLC-2基因是否与中国云南地区基诺族及汉族特发性全面强直-阵挛性癫癎(IGTCS)相关。方法以14例云南西双版纳傣族自治州景洪市基诺乡基诺族 IGTCS患者及其16名未发病亲属、67例云南籍汉族 IGTCS 患者及57名云南籍汉族健康体检者为对照,对常染色体3q26上 CLCN2基因的内含子2及外显子5、19(内含子18)进行研究,采用 PCR 及直接基因测序技术,应用病例-对照研究法对 CLCN2基因与云南基诺族及汉族 IGTCS 进行相关性分析。结果CLCN2基因的内含子2及外显子5、19在病例组和对照组中均没有发现已报道的易患突变,但我们在对外显子19的序列测定过程中发现了其上游内含子18的146位上存在1个单核苷酸多态性位点:146T→C。该位点的3种基因型(TT、TC、CC)在汉族病例组(9、3、29例)和汉族对照组(22、9、26例)之间的分布差异有统计学意义(x^2=16.079,P<0.05);在基诺族组(基诺族病例组+基诺族亲属组,6、12、12例)与汉族对照组(22、9、26例)之间分布差异亦有统计学意义(x^2=7.027,P<0.05)。汉族病例组与汉族对照组间 TT 型与非 TT 型基因型(分别为9、32例和22、35例)、TC 型与非 TC 型基因型(分别为3、38例和9、48例)比较差异有统计学意义(x^2=10.694,OR=4.121,P<0.05;x^2=11.592,OR=0.238,P<0.05)。结论 CLCN2基因内含子18的多态性位点 146T→C可能是中国云南地区基诺族与汉族 IGTCS 患者的1个相关性位点,且在本组有限的样本数量研究中,此 SNP 位点在两个民族 IGTCS 患者之间的分布无民族差异。基因型 TF 为 IGTCS 的1个保护性因素,基因型 TC则增加了患者的易患性。Objective To investigate whether the voltage-gated chloride channel CLC-2 gene-- CLCN2 is associated with idiopathic generalized tonic-clonic seizures （often called a grand mal seizure, GME） of Jinuo people and Han people from Yunnan province. Methods Three regions, including Intron 2, Exon 5 and Exon 19 （Intron 18）, of CLCN2 were selected to conduct sequence analysis. The case-control study design was used to detect association between gene polymorphism and idiopathic generalized tonicclonic seizures of Jinuo people and Han people from Yunnan province. Results No previously reported susceptible mutations were found in Intron 2, Exon 5 and Exon 19 in Jinuo people and Han people from Yunnan province. However we found a single nucleotide polymorphism （SNP） at site 146 of Intron 18. Case-control study were carried out, using this SNP. Distribution of the 3 genotypes （TT, TC, CC） has a significant difference between the IGTCS patients of Han people and the normal controls of Han people （9, 3, 29 cases and 22, 9, 26,respectively,Χ^2=16.079,P 〈 0.05） Distribution of the 3 genotypes （TT, TC, CC） has a significant difference between the Jinuo people （the IGTCS patients and their relatives） and the normal controls of Han people （6, 12, 12 cases and 22, 9, 26 cases,Χ^2 =7.027, P 〈0.05）. Distribution of the TT and non-TT gene type （9, 32 cases and 22, 35 cases）, TC and non-TC gene type （3, 38 cases and 9, 48 cases） has a significant difference between the IGTCS patients of Han people and the normal control of Han people （Χ^2 = 10. 694, P 〈 0. 05, OR = 4. 121;Χ^2 = 11. 592, P 〈 0.05, OR = 0. 238）. Conclusions The data shows that the SNP at site 146 of Intron 18 of CLCN2 might be a potential susceptible polymorphism causing idiopathic generalized tonic-clonic seizures in Han people and Jinuo people from Yunnan province, and there is no significant difference between the 2 group. The TT gene type plays a protect role in the IGTCS patients, however, the gene type TC increa

关 键 词：癫痫 强直阵挛性 氯化物通道 多态性 单核苷酸 病例对照研究 

分 类 号：R742.1[医药卫生—神经病学与精神病学]