Zheng Zhaoshi, Yan Yayun, Guo Qi, Wang Libo, Han Xuemei, Liu Songyan
No. 1 Department of Neurology, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130031, People's Republic of China.
Pharmgenomics Pers Med. 2021 Jan 14;14:77-86. doi: 10.2147/PGPM.S279664. eCollection 2021.
Long non-coding RNA H19 was highly expressed in the latent period of epilepsy, contributing to apoptosis of hippocampal neurons by targeting let-7b. Transforming growth factor beta receptor 1 (), a target of let-7b, is located on the susceptibility locus for epilepsy. In this context, we investigated the association between tagSNPs in long non-coding RNA and transforming growth factor beta receptor 1 () rs6478974 and the risk of epilepsy.
The present study consisted of 302 patients with epilepsy and 612 age- and gender-matched controls. The polymorphisms were analyzed using a TaqMan allelic genotyping assay. and mRNA levels were determined using quantitative real-time polymerase chain reaction.
The AT and TT genotypes emerged as a protective factor for the risk of epilepsy (AT vs AA: adjusted OR = 0.59, 95% CI: 0.39-0.89, = 0.01; TT vs AA: adjusted OR = 0.53, 95% CI: 0.35-0.80, = 0.002, respectively). The protective effect was also observed in recessive genetic model (adjusted OR = 0.56, 95% CI: 0.38-0.82, = 0.003). Individuals carrying the rs6478974 TT genotype had lower levels of mRNA. Moreover, the TCTAT and TCCAA haplotypes emerged as a risk factor for epilepsy and the rs3741219-rs2839698-rs6478974 was associated with an interactive effect on the risk of epilepsy.
The current study provides evidence of the rs6478974 TT genotype decreasing the susceptibility to epilepsy by reducing the levels of mRNA.
长链非编码RNA H19在癫痫潜伏期高表达，通过靶向let-7b促进海马神经元凋亡。转化生长因子β受体1（TGFβR1）是let-7b的一个靶点，位于癫痫易感基因座上。在此背景下，我们研究了长链非编码RNA H19标签单核苷酸多态性（tagSNPs）与转化生长因子β受体1（TGFβR1）rs6478974和癫痫风险之间的关联。
本研究纳入302例癫痫患者和612例年龄及性别匹配的对照。采用TaqMan等位基因基因分型检测法分析多态性。使用定量实时聚合酶链反应测定TGFβR1和H19 mRNA水平。
H19的AT和TT基因型是癫痫风险的保护因素（AT与AA相比：校正比值比=0.59，95%可信区间：0.39-0.89，P=0.01；TT与AA相比：校正比值比=0.53，95%可信区间：0.35-0.80，P=0.002）。在隐性遗传模型中也观察到了保护作用（校正比值比=0.56，95%可信区间：0.38-0.82，P=0.003）。携带rs6478974 TT基因型的个体TGFβR1 mRNA水平较低。此外，TCTAT和TCCAA单倍型是癫痫的危险因素，rs3741219-rs2839698-rs6478974与癫痫风险存在交互作用。
本研究提供了证据表明rs6478974 TT基因型通过降低TGFβR1 mRNA水平降低癫痫易感性。
