机构：[1]Department of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China[2]Guangdong Key Laboratory of Age-related Cardiac and Cerebral Diseases, Guangdong Medical University, Zhanjiang, Guangdong, China[3]Clinical Research Center, Guangdong Medical University, Zhanjiang, Guangdong, China[4]Emergency Department, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China[5]Department of Neurology, Beijing Tongren Hospital, Capital Medical University, Beijing, China临床科室神经内科首都医科大学附属北京同仁医院首都医科大学附属同仁医院[6]Department of Neurology, the First People’s Hospital of Pingdingshan, Pingdingshan, Hebei, China[7]Department of Neurology, Central People’s Hospital of Zhanjiang, Zhanjiang, Guangdong, China[8]Institute of Neurology, Guangdong Medical University, Zhanjiang, Guangdong, China[9]Stroke Center, Neurology& Neurosurgery Division, Clinical Medicine Research Institute & the First Affiliated Hospital, Jinan University, Guangzhou, Guangdong, China
D-serine is a predominant N-methyl-D-aspartate receptor co-agonist with glutamate, and excessive activation of the receptor plays a substantial role in epileptic seizures. Serine racemase (SRR) is responsible for transforming L-serine to D-serine. In this study, we aimed to investigate the genetic roles of SRR and a neighbouring gene, nonsense-mediated mRNA decay factor (SMG6), in temporal lobe epilepsy (TLE). Here, a total of 496 TLE patients and 528 healthy individuals were successfully genotyped for three SRR tag single nucleotide polymorphisms. The frequencies of the GG genotype at rs4523957 T > G were reduced in the TLE cases in the initial cohort (cohort 1) and were confirmed in the independent cohort (cohort 2). An analysis of all TLE cases in cohort 1 + 2 revealed that the seizure frequency and drug-resistant incidence were significantly decreased in carriers of the GG genotype at rs4523957. Intriguingly, the activity of the SMG6 promoter with the mutant allele at rs4523957 decreased by 22% in the dual-luciferase assay, and up-regulated expression of SMG6 was observed in an epilepsy rat model. This study provides the first demonstration that the GG genotype is a protective marker against TLE. In particular, variation at rs4523957 likely inhibits SMG6 transcription and plays a key role against susceptibility to and severity of TLE. The significance of SMG6 hyperfunction in epileptic seizures deserves to be investigated in future studies.
基金：
Postdoctoral Science Foundation of Guangdong Medical University [701z20150002]; National Natural Science Foundation of China (NSFC) [81271214, 81471294]
第一作者机构：[1]Department of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China[2]Guangdong Key Laboratory of Age-related Cardiac and Cerebral Diseases, Guangdong Medical University, Zhanjiang, Guangdong, China
共同第一作者：
通讯作者：
通讯机构：[8]Institute of Neurology, Guangdong Medical University, Zhanjiang, Guangdong, China[9]Stroke Center, Neurology& Neurosurgery Division, Clinical Medicine Research Institute & the First Affiliated Hospital, Jinan University, Guangzhou, Guangdong, China
推荐引用方式(GB/T 7714)：
Tao Hua,Zhou Xu,Xie Qian,et al.SRR intronic variation inhibits expression of its neighbouring SMG6 gene and protects against temporal lobe epilepsy[J].JOURNAL OF CELLULAR AND MOLECULAR MEDICINE.2018,22(3):1883-1893.doi:10.1111/jcmm.13473.
APA：
Tao, Hua,Zhou, Xu,Xie, Qian,Ma, Zhonghua,Sun, Fuhai...&Li, Keshen.(2018).SRR intronic variation inhibits expression of its neighbouring SMG6 gene and protects against temporal lobe epilepsy.JOURNAL OF CELLULAR AND MOLECULAR MEDICINE,22,(3)
MLA：
Tao, Hua,et al."SRR intronic variation inhibits expression of its neighbouring SMG6 gene and protects against temporal lobe epilepsy".JOURNAL OF CELLULAR AND MOLECULAR MEDICINE 22..3(2018):1883-1893
