Association between variation in the human KCNJ10 potassium ion channel gene and seizure susceptibility
Association between variation in the human KCNJ10 potassium ion channel gene and seizure susceptibility
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DOI：
10.1016/j.eplepsyres.2004.02.003
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发表时间：
2004-02-01
影响因子：
2.2
通讯作者：
Ferraro, TN
中科院分区：
文献类型：
--
作者：
Buono, RJ;Lohoff, FW;Ferraro, TN
目的：我们的研究计划使用遗传连锁和关联分析，以确定人类癫痫敏感性和抵抗等位基因。小鼠数量性状基因座定位导致钾离子通道基因Kcnj 10的遗传变异，暗示它是一个假定的癫痫易感基因。这项工作的目的是将这些动物模型数据转化为人类遗传关联研究。研究方法：我们使用单链构象多态性（SSCP）电泳，DNA测序和数据库搜索（NCBI），以确定在人类KCNJ 10基因的变异。限制性片段长度多态性（RFLP）分析。应用SSCP和焦磷酸测序（TM）技术对407例癫痫患者和284例正常对照者的KCNJ 10基因单核苷酸多态性（SNP，dbSNP rs#1130183）进行了基因分型。癫痫组包括难治性内侧颞叶癫痫（n = 153）、儿童缺失（n = 84）、青少年肌阵挛（n = 111）和未另行说明的特发性全身性癫痫（IGE-NOS，n = 59）患者，所有患者均为欧洲血统。结果：SNP rs#1130183（C > T）将氨基酸271（379）从精氨酸改变为半胱氨酸（R271 C）。C等位基因（Arg）是常见的，与癫痫患者相比，对照组转换为T等位基因（Cys）的频率是癫痫患者的两倍。列联分析证明癫痫抵抗与等位基因频率之间存在统计学显著相关性，Mantel-Haenszel卡方= 5.65，d. f。= 1，P = 0.017，比值比0.52，95%CI 0.33-0.82。结论：当将常见形式的局灶性和全身性癫痫作为一组进行分析时，SNP rs#1130183的T等位基因与癫痫发作抵抗相关。这些数据表明，KCNJ 10的这种错义变异（或附近的变异）与人类全身性癫痫发作的易感性有关。(C)2004 Elsevier B. V.保留所有权利。
Purpose: Our research program uses genetic linkage and association analysis to identify human seizure sensitivity and resistance alleles. Quantitative trait loci mapping in mice led to identification of genetic variation in the potassium ion channel gene Kcnj10, implicating it as a putative seizure susceptibility gene. The purpose of this work was to translate these animal model data to a human genetic association study. Methods: We used single stranded conformation polymorphism (SSCP) electrophoresis, DNA sequencing and database searching (NCBI) to identify variation in the human KCNJ10 gene. Restriction fragment length polymorphism (RFLP) analysis. SSCP and Pyrosequencing(TM) Were used to genotype a single nucleotide polymorphism (SNP, dbSNP rs#1130183) in KCNJ10 in epilepsy patients (n = 407) and unrelated controls (n = 284). The epilepsy group was comprised of patients with refractory mesial temporal lobe epilepsy (n = 153), childhood absence (n = 84), juvenile myoclonic (n = I 11) and idiopathic generalized epilepsy not otherwise specified (IGE-NOS, n = 59) and all were of European ancestry. Results: SNP rs#1130183 (C > T) alters amino acid 271 (of 379) from an arginine to a cysteine (R271C). The C allele (Arg) is common with conversion to the T allele (Cys) occurring twice as often in controls compared to epilepsy patients. Contingency analysis documented a statistically significant association between seizure resistance and allele frequency, Mantel-Haenszel chi square = 5.65, d.f. = 1, P = 0.017, odds ratio 0.52, 95% CI 0.33-0.82. Conclusion: The T allele of SNP rs#1130183 is associated With seizure resistance when common forms of focal and generalized epilepsy are analyzed as a group. These data suggest that this missense variation in KCNJ10 (or a nearby variation) is related to general seizure susceptibility in humans. (C) 2004 Elsevier B.V. All rights reserved.