Molecular Medicine Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.
Urogenital Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
J Mol Neurosci. 2020 Jul;70(7):1050-1055. doi: 10.1007/s12031-020-01504-z. Epub 2020 Feb 26.
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.
多发性硬化症(MS)是一种复杂的遗传特征,其特征是中枢神经系统(CNS)脱髓鞘、炎症和进行性神经功能障碍。有证据表明自噬和应激机制与 MS 紧密相关。先前的研究表明,LncRNA TRPM2-AS 和 HNF1A-AS1 分别参与氧化应激和自噬。在本研究中,我们调查了 TRPM2-AS 和 HNF1A-AS1 单核苷酸多态性(SNP)与 300 名伊朗患者和 300 名健康对照者 MS 风险的关联。我们的研究结果表明,与健康对照组相比,MS 患者中 rs933151 的 T 等位基因明显较少(OR(95%CI)=0.696(0.532-0.911),P=0.005)。该 SNP 在共显性和显性模型中与较低的 MS 风险相关(OR(95%CI)=0.68(0.48-0.96),P 值=0.032;OR(95%CI)=0.65(0.47-0.91),P 值=0.012,分别)。在任何遗传模型中,rs7953249 与 MS 易感性均无关联(共显性、显性、隐性和超显性模型的 P 值分别为 0.73、0.46、0.61 和 0.71)。本研究强调了 TRPM2-AS 基因(SNP rs933151)与 MS 易感性的新关联。