Senousy Mahmoud A, Shaker Olfat G, Sayed Noha H, Fathy Nevine, Kortam Mona A
Biochemistry Department, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.
Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Cairo University, Cairo 11562, Egypt.
ACS Chem Neurosci. 2020 Jun 3;11(11):1651-1660. doi: 10.1021/acschemneuro.0c00150. Epub 2020 May 12.
The pathogenesis of multiple sclerosis (MS) is influenced by the interaction of genetic and epigenetic mechanisms. The long noncoding RNA GAS5 acts as a competing endogenous RNA for microRNA-137 and is involved in demyelination. We investigated the association of GAS5 and miR-137 expression and their polymorphisms with MS susceptibility. One hundred and eight MS patients and 104 healthy controls were included. Expression analysis and genotyping of GAS5-rs2067079 and miR-137-rs1625579 single nucleotide polymorphisms were performed by qPCR. Serum GAS5 was upregulated, while serum miR-137 was downregulated in MS compared with the controls. Serum miR-137 was an excellent discriminator of MS patients from the controls (AUC = 0.97) and a negative independent predictor of MS in multivariate logistic analysis. Serum GAS5 expression was positively correlated with the expanded disability status scale scores in the relapsing-remitting MS patients. The rs2067079TT minor homozygote genotype was associated with an increased MS risk, while the rs1625579G minor allele was protective. rs1625579 showed an age-specific effect, while the rs2067079 affected the MS risk in gender- and age-specific manners. In MS patients, rs2067079TT was associated with a higher serum GAS5 than other genotypes, while serum miR-137 did not differ between rs1625579 genotypes. Our results suggest serum GAS5 and miR-137 as MS biomarkers, with miR-137 as a negative predictor of MS risk and GAS5 as a marker of MS severity. We propose rs2067079 and rs1625579 as novel genetic markers of MS susceptibility, and at least, rs2067079 possibly impacts the crosstalk between GAS5 and miR-137.
多发性硬化症（MS）的发病机制受遗传和表观遗传机制相互作用的影响。长链非编码RNA GAS5作为微小RNA-137的竞争性内源性RNA，参与脱髓鞘过程。我们研究了GAS5和miR-137的表达及其多态性与MS易感性的关联。纳入了108例MS患者和104例健康对照。通过qPCR对GAS5-rs2067079和miR-137-rs1625579单核苷酸多态性进行表达分析和基因分型。与对照组相比，MS患者血清GAS5上调，而血清miR-137下调。血清miR-137是区分MS患者与对照组的优秀指标（AUC = 0.97），在多因素逻辑分析中是MS的负性独立预测因子。复发缓解型MS患者血清GAS5表达与扩展残疾状态量表评分呈正相关。rs2067079TT纯合子基因型与MS风险增加相关，而rs1625579G次要等位基因具有保护作用。rs1625579显示出年龄特异性效应，而rs2067079以性别和年龄特异性方式影响MS风险。在MS患者中，rs2067079TT基因型的血清GAS5高于其他基因型，而rs1625579各基因型之间的血清miR-137无差异。我们的结果表明血清GAS5和miR-137可作为MS生物标志物，miR-137作为MS风险的负性预测因子，GAS5作为MS严重程度的标志物。我们提出rs2067079和rs1625579作为MS易感性的新型遗传标志物，至少rs2067079可能影响GAS5和miR-137之间的相互作用。
