SCN1A基因多态性与婴儿痉挛症及促肾上腺皮质激素反应性的关联

Association of SCN1A gene polymorphisms with infantile spasms and adrenocorticotropic hormone responsiveness.

作者信息

Zhang Y, Zou L-P, Ding Y-X, He B, Yang G

机构信息

Department of Pediatrics, Chinese PLA General Hospital (No. 301 Hospital of PLA), Beijing, China.

出版信息

Eur Rev Med Pharmacol Sci. 2014;18(17):2500-6.

PMID:25268096

Abstract

OBJECTIVES

Infantile spasms (IS) are severe epileptic encephalopathy during infancy. The SCN1A encodes the α1 subunit of the neuronal voltage-gated sodium channels, and mutations in SCN1A have been frequently detected in idiopathic epilepsy and encephalopathy, which had similar symptoms as IS. Therefore, we investigated the association of SCN1A polymorphism with the IS and the responsiveness to adrenocorticotropic hormone (ACTH) treatment in the present study.

PATIENTS AND METHODS

We totally collected 113 IS patients and and 122 age-matched healthy controls. All of the subjects were Han Chinese descent, and the 113 cases were further divided into subgroups of cryptogenic and symptomatic patients. Nine tag SNPs within the SCN1A gene were selected and genotyped by the direct sequencing of PCR-amplified products. The ACTH was then applied to all of the cases.

RESULTS

Two SNPs in high linkage disequilibrium, rs13397210 and rs760543, were significantly associated with IS under genotype model (p = 0.015). In addition, we also found that a 4-SNP haplotype (CAGC) which contains the aforementioned 2 SNPs, was associated with increased responsiveness to ACTH therapy in IS (p = 0.018, OR = 4.8) under recessive model. Of the 2 subgroups of cases, more cryptogenic patients responded to the ACTH treatment than the symptomatic patients.

CONCLUSIONS

The results suggested that genetic variants of the SCN1A gene were associated with IS and ACTH responsiveness.

摘要

目的

婴儿痉挛症（IS）是婴儿期严重的癫痫性脑病。SCN1A基因编码神经元电压门控钠通道的α1亚基，在特发性癫痫和脑病中经常检测到SCN1A基因的突变，这些疾病具有与IS相似的症状。因此，在本研究中我们调查了SCN1A基因多态性与IS以及促肾上腺皮质激素（ACTH）治疗反应性之间的关联。

患者与方法

我们共收集了113例IS患者和122例年龄匹配的健康对照。所有受试者均为汉族，113例患者进一步分为隐源性和症状性患者亚组。选择SCN1A基因内的9个标签单核苷酸多态性（SNPs），通过对聚合酶链反应（PCR）扩增产物进行直接测序来进行基因分型。然后对所有病例应用ACTH。

结果

处于高度连锁不平衡状态的两个SNPs，rs13397210和rs760543，在基因型模型下与IS显著相关（p = 0.015）。此外，我们还发现一个包含上述两个SNPs的4-SNP单倍型（CAGC），在隐性模型下与IS患者对ACTH治疗的反应性增加相关（p = 0.018，比值比[OR]=4.8）。在2个病例亚组中，隐源性患者对ACTH治疗的反应比症状性患者更多。