He Ni, Tian Liting, Jin Jingnan, Liu Yue, Li Lifang, Wang Xiaokun, Li Danyang, Wang Xia, Li Xiaoju, Chen Zihong, Zhang Lanxin, Qiao Lukuan, Ning Shangwei, Wang Lihua, Wang Jianjian
Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Faculty of Computing, Harbin Institute of Technology, Harbin, China.
Noncoding RNA Res. 2024 Dec 31;11:209-219. doi: 10.1016/j.ncrna.2024.12.012. eCollection 2025 Apr.
Myasthenia gravis (MG) is an autoimmune disorder caused by antibodies that target the postsynaptic muscle membrane. Recent evidence suggests that genetic variants and long noncoding RNAs (lncRNAs) play crucial roles in the pathogenesis of MG. The purpose of this study was to investigate the associations between lncRNA-related single-nucleotide polymorphisms (SNPs) and MG susceptibility in Chinese populations.
First, we identified lncRNA mutation hotspot regions based on the improved Kolmogorov‒Smirnov test and the cumulative hypergeometric distribution principle. Next, we further identified lncRNA mutation hotspot SNPs by calculating conservative scores. Finally, experiments were conducted to verify the associations between lncRNA mutation hotspot SNPs and MG susceptibility. A total of 82 patients with MG and 82 healthy controls were recruited for genotyping of lncRNA mutation hotspot SNPs using the SNaPshot technique. Quantitative real-time PCR was used to investigate lncRNA expression in 34 patients with MG and 37 healthy controls.
In the multistep calculation, 14 candidate SNPs of 3 lncRNAs (AL031686.1, NONHSAT028539.2 and AC245014.3) in MG were identified as mutation hotspot SNPs. The genotyping results of the 14 SNPs in our study revealed no statistically significant differences in the frequencies of genotypes and alleles between patients with MG and controls. However, in the lncRNA AL031686.1, rs1000383 and rs6094353 were in perfect linkage disequilibrium (LD) and were associated with an increased risk of ocular MG. Additionally, rs6094347 was associated with an increased risk of ocular MG. Nevertheless, no SNP was found to be associated with factors such as sex, age, the presence or absence of thymoma, or the genetic model of MG. Further experiments revealed that NONHSAT028539.2 expression was upregulated in peripheral blood mononuclear cells (PBMCs) from patients with MG compared with those from healthy controls.
In our study, we did not find an association between the 14 mutation hotspot SNPs of lncRNAs and susceptibility to MG. However, we observed that the rs6094347 and rs1000383/rs6094353 polymorphisms in the lncRNA AL031686.1 were associated with the risk of ocular MG.
重症肌无力（MG）是一种自身免疫性疾病，由靶向突触后肌膜的抗体引起。最近的证据表明，基因变异和长链非编码RNA（lncRNA）在MG的发病机制中起关键作用。本研究的目的是调查lncRNA相关单核苷酸多态性（SNP）与中国人群MG易感性之间的关联。
首先，基于改进的Kolmogorov-Smirnov检验和累积超几何分布原理确定lncRNA突变热点区域。接下来，通过计算保守得分进一步确定lncRNA突变热点SNP。最后，进行实验验证lncRNA突变热点SNP与MG易感性之间的关联。共招募了82例MG患者和82名健康对照，使用SNaPshot技术对lncRNA突变热点SNP进行基因分型。采用定量实时PCR检测34例MG患者和37名健康对照外周血单个核细胞（PBMC）中lncRNA的表达。
在多步计算中，MG中3个lncRNA（AL031686.1、NONHSAT028539.2和AC245014.3）的14个候选SNP被确定为突变热点SNP。本研究中14个SNP的基因分型结果显示，MG患者与对照组之间的基因型和等位基因频率无统计学显著差异。然而，在lncRNA AL031686.1中，rs1000383和rs6094353处于完全连锁不平衡（LD）状态，与眼肌型MG风险增加相关。此外，rs6094347与眼肌型MG风险增加相关。然而，未发现SNP与性别、年龄、胸腺瘤的有无或MG的遗传模式等因素相关。进一步实验显示，与健康对照相比，MG患者外周血单个核细胞（PBMC）中NONHSAT028539.2的表达上调。
在本研究中，我们未发现lncRNA的14个突变热点SNP与MG易感性之间存在关联。然而，我们观察到lncRNA AL031686.1中的rs6094347和rs1000383/rs6094353多态性与眼肌型MG风险相关。
