In:
Journal of Cellular and Molecular Medicine, Wiley, Vol. 22, No. 3 ( 2018-03), p. 1883-1893
Abstract:
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 ( SMG 6), 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 SMG 6 promoter with the mutant allele at rs4523957 decreased by 22% in the dual‐luciferase assay, and up‐regulated expression of SMG 6 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 SMG 6 transcription and plays a key role against susceptibility to and severity of TLE . The significance of SMG 6 hyperfunction in epileptic seizures deserves to be investigated in future studies.
Type of Medium:
Online Resource
ISSN:
1582-1838
,
1582-4934
DOI:
10.1111/jcmm.2018.22.issue-3
Language:
English
Publisher:
Wiley
Publication Date:
2018
detail.hit.zdb_id:
2076114-4
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