Contents lists available at ScienceDirect Gene Reports journal homepage: www.elsevier.com/locate/genrep Peripheral expression of Rubicon Like Autophagy Enhancer is reduced in epileptic patients Sara Mirzajani a , Soudeh Ghafouri-Fard a , Jafar Mehvari Habibabadi b , Shahram Arsang-Jang c , Mir Davood Omrani a , Seyed Sohrab Hashemi Fesharaki d , Arezou Sayad a, ⁎ , Mohammad Taheri d, ⁎ a Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran b Isfahan Neuroscience Research Center, Isfahan University of Medical Sciences, Isfahan, Iran c Clinical Research Development Center (CRDU), Qom University of Medical Sciences, Qom, Iran d Urogenital Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran ARTICLE INFO Keywords: Rubicon Like Autophagy Enhancer RUBCNL Epilepsy Refractory ABSTRACT Epilepsy is regarded as a common neurological disorder which affects about 1% of general population. Dysregulation of several signaling pathways has been reported in epileptic patients. In the present study, we examined peripheral expression of an autophagy associated gene namely Rubicon Like Autophagy Enhancer (RUBCNL) in 80 epileptic patients (40 refractory and 40 non-refractory ones) and 40 normal persons. Expression of RUBCNL was significantly lower in refractory group compared with controls (Posterior beta of relative ex- pression (RE) = -1.617, P value < 0.0001). Moreover, expression of this gene was lower in non-refractory patients compared with controls (Posterior beta of RE = -1.634, P value < 0.0001). However, expression of RUBCNL was not different between refractory and non-refractory patients. Differences between non-refractory and control groups were detected in both female and male subgroup analyses. However, difference between male refractory and male control groups was not significant. Expression of RUBCNL was not correlated with age of study participants (P = 0.725). Transcript levels of RUBCNL could differentiate refractory group from controls with diagnostic power of 0.803. Transcript levels of this gene could discriminate non-refractory group from controls with diagnostic power of 0.887. However, RUBCNL could not differentiate non-refractory group from refractory ones (Area under curve = 0.541, P = 0.535). The current study shows dysregulation of an autophagy- associated gene in peripheral blood of epileptic patients and demonstrates its possible application as a bio- marker. 1. Introduction Epilepsy is a severe neurological disorder which is linked with stigma (Fiest et al., 2014), presence of other psychiatric conditions (Tellez-Zenteno et al., 2007), and economic burden (Begley and Beghi, 2002). Based on the Global Burden of Disease 2016 Study (2017), epilepsy is the third most troublesome disorder among the neurological disorders. Genetic factors participate in the development of epilepsy (Mazdeh et al., 2018). Among the identified factors are deleterious mutations in genes coding ion channels, neurotransmitters and proteins implicated in the neuronal functions (Ebrahimi et al., 2010; Tafakhori et al., 2015). Besides, certain structural chromosomal abnormalities have been associated with disorder (Tafakhori et al., 2015). Dysregulation of a number of signaling pathways and genes has been associated with epileptic seizures (Bozzi et al., 2011). Among these cellular functions is autophagy (Giorgi et al., 2015). The first evidence pointing to the role of autophagy in epilepsy has come from the ob- served effect of the autophagy enhancer rapamycin in modulation of epileptic phenotypes (Wong, 2011). The mammalian target of rapa- mycin (mTOR) pathway which is associated with autophagy has been shown to participate in the pathogenesis of diverse kinds of epilepsy (Wong, 2010). Animal studies have shown disinhibition of mTOR in forebrain neurons results in both occurrence of seizure and compro- mised autophagy (Mcmahon et al., 2012). In line with this observation, increased mTOR activation and decreased autophagy have been de- tected in brain samples from human patients with tuberous sclerosis https://doi.org/10.1016/j.genrep.2019.100539 Received 30 September 2019; Received in revised form 10 October 2019; Accepted 11 October 2019 Abbreviation: RUBCNL, Rubicon Like Autophagy Enhancer; RE, relative expression; mTOR, mammalian target of rapamycin; MRI, magnetic resonance imaging; DW, diffusion weighted; AUC, area under curve; PUFA, polyunsaturated fatty acids alone ⁎ Corresponding authors. E-mail addresses: ar.sayad@yahoo.com (A. Sayad), mohammad_823@yahoo.com (M. Taheri). Gene Reports 17 (2019) 100539 Available online 22 October 2019 2452-0144/ © 2019 Published by Elsevier Inc. T