Abstract
Multiple sclerosis (MS) is a complex genetic trait characterized by demyelination of central nervous system (CNS), inflammation, and progressive neurological dysfunction. There is evidenced that autophagy and stress mechanisms are tightly linked with MS. Previous studies have demonstrated that LncRNAs TRPM2-AS and HNF1A-AS1 are involved in oxidative stress and autophagy, respectively. In the current study, we investigated the association of TRPM2-AS and HNF1A-AS1 single nucleotide polymorphisms (SNPs) with MS risk in 300 Iranian patients and 300 healthy controls. Our results have shown that T allele of the rs933151 was statistically significant underrepresented in MS patients compared with healthy subjects (OR (95% CI) = 0.696 (0.532–0.911), P = 0.005). This SNP was associated with lower MS risk in codominant and dominant models (OR (95% CI) = 0.68 (0.48–0.96), P value = 0.032; OR (95% CI) = 0.65 (0.47–0.91), P value = 0.012, respectively). The rs7953249 was not associated with MS susceptibility in any inheritance models (P values of 0.73, 0.46, 0.61, and 0.71 for codominant, dominant, recessive, and overdominant models, respectively). Present study highlighted a novel association at the TRPM2-AS gene (SNP rs933151) with MS susceptibility.
Similar content being viewed by others
References
Chastain EM, Miller SD (2012) Molecular mimicry as an inducing trigger for CNS autoimmune demyelinating disease. Immunol Rev 245:227–238. https://doi.org/10.1111/j.1600-065X.2011.01076.x
Clapham DE (2003) TRP channels as cellular sensors. Nature 426:517. https://doi.org/10.1038/nature02196
Compston A, Coles A (2008) Multiple sclerosis. Lancet (British edition) 372:1502–1517
Consortium WTCC (2007) Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447:661–678. https://doi.org/10.1038/nature05911
Dastmalchi R, Ghafouri-Fard S, Omrani MD, Mazdeh M, Sayad A, Taheri M (2018) Dysregulation of long non-coding RNA profile in peripheral blood of multiple sclerosis patients. Mult Scler Relat Disord 25:219–226. https://doi.org/10.1016/j.msard.2018.07.044
Demirci S, Demirci S, Kutluhan S, Koyuncuoglu HR, Yurekli VA (2016) The clinical significance of the neutrophil-to-lymphocyte ratio in multiple sclerosis international. Int J Neurosci 126:700–706. https://doi.org/10.3109/00207454
Ding C-H, Yin C, Chen SJ, Wen LZ, Ding K, Lei SJ, Liu JP, Wang J, Chen KX, Jiang HL, Zhang X, Luo C, Xie WF (2018) The HNF1α-regulated lncRNA HNF1A-AS1 reverses the malignancy of hepatocellular carcinoma by enhancing the phosphatase activity of SHP-1. Mol Cancer 17:63. https://doi.org/10.1186/s12943-018-0813-1
Eftekharian MM, Ghafouri-Fard S, Soudyab M, Omrani MD, Rahimi M, Sayad A, Komaki A, Mazdeh M, Taheri M (2017) Expression analysis of long non-coding RNAs in the blood of multiple sclerosis patients. J Mol Neurosci 63:333–341. https://doi.org/10.1007/s12031-017-0982-1
Fonfria E, Marshall IC, Boyfield I, Skaper SD, Hughes JP, Owen DE, Zhang W, Miller BA, Benham CD, McNulty S (2005) Amyloid β-peptide (1–42) and hydrogen peroxide-induced toxicity are mediated by TRPM2 in rat primary striatal cultures. J Neurochem 95:715–723. https://doi.org/10.1111/j.1471-4159.2005.03396.x
Gianfrancesco MA, Barcellos LF (2016) Obesity and multiple sclerosis susceptibility: a review. J Neurol Neuromed 1:1. https://doi.org/10.29245/2572.942x/2016/7.1064
Gonsette R (2008) Neurodegeneration in multiple sclerosis: the role of oxidative stress and excitotoxicity. J Neurol Sci 274:48–53. https://doi.org/10.1016/j.jns.2008.06.029
Heikkilä K, Silander K, Salomaa V, Jousilahti P, Koskinen S, Pukkala E, Perola M (2011) C-reactive protein-associated genetic variants and cancer risk: findings from FINRISK 1992, FINRISK 1997 and health 2000 studies. Eur J Cancer 47:404–412. https://doi.org/10.1016/j.ejca.2010.07.032
Hu Y et al (2014) A long non-coding RNA signature to improve prognosis prediction of colorectal. Oncotarget 5:2230. https://doi.org/10.18632/oncotarget.1895
Huang C et al (2017) Downregulation of a novel long noncoding RNA TRPM2-AS promotes apoptosis in non–small cell lung cancer. Tumor Biol 39. https://doi.org/10.1177/1010428317691191
Keytsman C, Eijnde BO, Hansen D, Verboven K, Wens I (2017) Elevated cardiovascular risk factors in multiple sclerosis. Mult Scler Relat Disord 17:220–223. https://doi.org/10.1016/j.msard.2017.08.011
Kroemer G, Mariño G, Levine B (2010) Autophagy and the integrated stress response. Mol Cell 40:280–293. https://doi.org/10.1016/j.molcel.2010.09.023
Liang P, Le W (2015) Role of autophagy in the pathogenesis of multiple sclerosis. Neurosci Bull 31:435–444. https://doi.org/10.1007/s12264-015-1545-5
Ma L, Xie XW, Ma L, Pang JL, Xiong XM, Zheng HD, Shen XL, Wen ZG, Wang HY (2017) Downregulated long non-coding RNA TRPM2-AS inhibits cisplatin resistance of non-small cell lung cancer cells via activation of p53-p66shc pathway. Eur Rev Med Pharmacol Sci 21:2626–2634
Motori E et al (2013) Inflammation-induced alteration of astrocyte mitochondrial dynamics requires autophagy for mitochondrial network maintenance. Cell Metab 18:844–859. https://doi.org/10.1016/j.cmet.2013.11.005
Orfanelli U, Jachetti E, Chiacchiera F, Grioni M, Brambilla P, Briganti A, Freschi M, Martinelli-Boneschi F, Doglioni C, Montorsi F, Bellone M, Casari G, Pasini D, Lavorgna G (2015) Antisense transcription at the TRPM2 locus as a novel prognostic marker and therapeutic target in prostate cancer. Oncogene 34(2015):2094–2102. https://doi.org/10.1038/onc.2014.144
Perraud A-L, Takanishi CL, Shen B, Kang S, Smith MK, Schmitz C, Knowles HM, Ferraris D, Li W, Zhang J, Stoddard BL, Scharenberg AM (2005) Accumulation of free ADP-ribose from mitochondria mediates oxidative stress-induced gating of TRPM2 cation channels. J Biol Chem 280:6138–6148. https://doi.org/10.1074/jbc.M411446200
Polman CH, Reingold SC, Banwell B, Clanet M, Cohen JA, Filippi M, Fujihara K, Havrdova E, Hutchinson M, Kappos L, Lublin FD, Montalban X, O'Connor P, Sandberg-Wollheim M, Thompson AJ, Waubant E, Weinshenker B, Wolinsky JS (2011) Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 69:292–302. https://doi.org/10.1002/ana.22366
Radi E, Formichi P, Battisti C, Federico A (2014) Apoptosis and oxidative stress in neurodegenerative diseases. J Alzheimers Dis 42:S125–S152. https://doi.org/10.3233/JAD-132738
Reiner AP et al (2008) Polymorphisms of the HNF1A gene encoding hepatocyte nuclear factor-1α are associated with C-reactive protein. J Hum Genet 82:1193–1201. https://doi.org/10.1016/j.ajhg.2008.03.017
Ridker PM, Pare G, Parker A, Zee RY, Danik JS, Buring JE, Kwiatkowski D, Cook NR, Miletich JP, Chasman DI (2008) Loci related to metabolic-syndrome pathways including LEPR, HNF1A, IL6R, and GCKR associate with plasma C-reactive protein: the women’s genome health study. Am J Hum Genet 82:1185–1192. https://doi.org/10.1016/j.ajhg.2008.03.015
Riva P, Ratti A, Venturin M (2016) The long non-coding RNAs in neurodegenerative diseases: novel mechanisms of pathogenesis. Curr Alzheimer Res 13:1219–1231
Roche S et al (2007) Candidate gene analysis of 21q22: support for S100B as a susceptibility gene for bipolar affective disorder with psychosis. Am J Med Genet B 144:1094–1096. https://doi.org/10.1002/ajmg.b.30556
Shen J, Siegel AB, Remotti H, Wang Q, Shen Y, Santella RM (2015) Deregulated long non-coding RNAs in hepatocellular carcinoma (HCC). AACR. https://doi.org/10.3390/cancers7030865
Shi H, Leng S, Liang H, Zheng Y, Chen L (2016) Association study of C-reactive protein associated gene HNF1A with ischemic stroke in Chinese population. BMC Med Genet 17:51. https://doi.org/10.1186/s12881-016-0313-3
Shu Y et al (2017) Association of serum gamma-glutamyltransferase and C-reactive proteins with neuromyelitis optica and multiple sclerosis. Mult Scler Relat Disord 18:65–70. https://doi.org/10.1016/j.msard.2017.09.021
Tully M, Shi R (2013) New insights in the pathogenesis of multiple sclerosis—role of acrolein in neuronal and myelin damage international. Int J Mol Sci 14:20037–20047. https://doi.org/10.3390/ijms141020037
Van Horssen J, Witte ME, Schreibelt G, De Vries HE (2011) Radical changes in multiple sclerosis pathogenesis. BBA-Mol Basis Dis 1812:141–150. https://doi.org/10.1016/j.bbadis.2010.06.011
Xu C, Huang Q, Zhang C, Xu W, Xu G, Zhao X, Liu X, du Y (2018) Long non-coding RNA TRPM2-AS AS a potential biomarker for hepatocellular carcinoma. Ir J Med Sci 187:621–628. https://doi.org/10.1007/s11845-017-1692-y
Yuan X, Waterworth D, Perry JR, Lim N, Song K, Chambers JC, Zhang W, Vollenweider P, Stirnadel H, Johnson T, Bergmann S, Beckmann ND, Li Y, Ferrucci L, Melzer D, Hernandez D, Singleton A, Scott J, Elliott P, Waeber G, Cardon L, Frayling TM, Kooner JS, Mooser V (2008) Population-based genome-wide association studies reveal six loci influencing plasma levels of liver enzymes. Am J Hum Genet 83:520–528. https://doi.org/10.1016/j.ajhg.2008.09.012
Zhou X-j et al (2011) Genetic association of PRDM1-ATG5 intergenic region and autophagy with systemic lupus erythematosus in a Chinese population. Ann Rheum Dis 70:1330–1337
Zhu W, Zhuang P, Song W, Duan S, Xu Q, Peng M, Zhou J (2017) Knockdown of lncRNA HNF1A-AS1 inhibits oncogenic phenotypes in colorectal carcinoma. Mol Med Rep 16:4694–4700. https://doi.org/10.3892/mmr.2019.10373
Zhuang C, Zheng L, Wang P (2018) Prognostic role of long non-coding rna hnF1a-as1 in chinese cancer patients: a meta-analysis. Oncotargets Ther 11:5325–5332. https://doi.org/10.2147/OTT.S163575
Funding
This research was supported by grant (grant No. JP-9309) from Education Office, Pasteur Institute of Iran.
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Conflict of Interest
The authors declared no potential conflicts of interest.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Bahrami, T., Taheri, M., Omrani, M.D. et al. Associations Between Genomic Variants in lncRNA-TRPM2-AS and lncRNA-HNF1A-AS1 Genes and Risk of Multiple Sclerosis. J Mol Neurosci 70, 1050–1055 (2020). https://doi.org/10.1007/s12031-020-01504-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12031-020-01504-z