Contents lists available at ScienceDirect Neuroscience Letters journal homepage: www.elsevier.com/locate/neulet Research article GAS5 genomic variants and risk of multiple sclerosis Mohammad Mahdi Eftekharian a , Rezvan Noroozi b,c , Alireza Komaki a , Mehrdokht Mazdeh a,d , Mohammad Taheri e, ⁎ , Soudeh Ghafouri-Fard b, ⁎ a Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran b Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran c Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran d Department of Neurology, Hamadan University of Medical Sciences, Hamadan, Iran e Urogenital Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran ARTICLE INFO Keywords: GAS5 lncRNA Multiple sclerosis ABSTRACT The lncRNA Growth arrest-specific5 (GAS5) has crucial roles in the apoptosis, suppression of cell growth and regulation of response to glucocorticoids. Previous studies have demonstrated its role in the pathogenesis of some immune-related disorders such as systemic lupus erythematosus and multiple sclerosis (MS). In the current study, we genotyped two possibly functional GAS5 polymorphisms (rs2067079 and rs6790) in 810 individuals including 410 MS patients and 400 age and sex-matched healthy subjects. There was a significant over-re- presentation of the rs2067079 T allele in MS patients compared with healthy individuals (OR (95% CI) = 1.38 (1.12–1.71), adjusted P value = 0.008). This SNP was associated with MS risk in co-dominant and recessive models (OR (95% CI) = 2.70 (1.54–4.76), adjusted P value = 0.003; OR (95% CI) = 2.58 (1.5–4.42), adjusted P value = 7.9E-4 respectively). The rs6790 was not associated with MS risk in any inheritance models. The T G haplotype (rs2067079 and rs6790 respectively) was significantly more prevalent among cases compared with controls (OR (95% CI) = 1.48 (1.16–1.89), adjusted P value = 0.005). Our results further highlight the role of GAS5 in the pathogenesis of MS. 1. Introduction Multiple sclerosis (MS) as a debilitating disorder of the central nervous system (CNS) is strongly associated with dysregulation of im- mune responses [1]. Demyelinated CNS plaques are considered as the most prominent feature of this disorder. Typically, these plaques con- tain a hypocellular zone marked by the presence of T cells, B lympho- cytes, plasma cells, and macrophages in perivascular regions. These immune cells can trigger an inflammatory cascade resulting in tissue damage, demyelination, and neurological defects [2]. The role of long non-coding RNAs (lncRNAs) in the modulation of such inflammatory responses or cytokine expression has been recently acknowledged [3]. The lncRNA Growth arrest-specific5 (GAS5) has crucial roles in the apoptosis and suppression of cell growth [4]. Its expression has been significantly decreased in a number of human malignancies [4] and increased in osteoarthritis chondrocytes [5]. More recently, Suo et al. have found GAS5 over-expression in CD4 + T cells of patients with systemic lupus erythematosus (SLE) compared with healthy individuals. The authors suggest GAS5 expression in CD4 + T cells as a putative biomarker for diagnosis and follow-up of SLE patients [6]. We have recently reported up-regulation of GAS5 expression in peripheral blood of MS patients compared with healthy subjects and proposed a role for this lncRNA in the molecular pathology of MS [7]. This gene contains a number of potentially functional polymorphisms including rs2067079 and rs6790. These single nucleotide polymorphisms (SNPs) are located in the promoter region of GAS5, act as enhancers and have been sug- gested as predictive biomarkers for chemoradiotherapy induced toxic reactions in nasopharyngeal cancer patients [8]. Based on the predicted role of these SNPs as expression Quantitative Trait Locus (e-QTL) [8] and our recent report of up-regulation of GAS5 in MS patients [7], we hypothesized that these SNPs might contribute in MS risk. To further validate our hypothesis, we designed the current case-control study to genotype these SNPs in Iranian MS patients and healthy individuals. 2. Material and methods 2.1. Study participants A total of 810 participants including 410 MS patients and 400 age and sex-matched healthy subjects participated in the current study. All https://doi.org/10.1016/j.neulet.2019.02.028 Received 12 October 2018; Received in revised form 20 January 2019; Accepted 18 February 2019 ⁎ Corresponding authors. E-mail addresses: mohammad.taheri@sbmu.ac.ir (M. Taheri), s.ghafourifard@sbmu.ac.ir (S. Ghafouri-Fard). Neuroscience Letters 701 (2019) 54–57 Available online 18 February 2019 0304-3940/ © 2019 Elsevier B.V. All rights reserved. T