重症肌无力易感性相关lncRNA突变热点snp的鉴定与验证

IF 5.9 3区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Non-coding RNA Research Pub Date : 2024-12-31 DOI:10.1016/j.ncrna.2024.12.012

Ni He , Liting Tian , Jingnan Jin , Yue Liu , Lifang Li , Xiaokun Wang , Danyang Li , Xia Wang , Xiaoju Li , Zihong Chen , Lanxin Zhang , Lukuan Qiao , Shangwei Ning , Lihua Wang , Jianjian Wang

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引用次数: 0

摘要

背景：重症肌无力（MG）是一种由靶向突触后肌膜的抗体引起的自身免疫性疾病。最近的证据表明，遗传变异和长链非编码rna （lncRNAs）在MG的发病机制中起着至关重要的作用。本研究旨在探讨中国人群中lncrna相关单核苷酸多态性（snp）与MG易感性之间的关系。方法：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，我们通过计算保守分数进一步鉴定lncRNA突变热点snp。最后，通过实验验证lncRNA突变热点snp与MG易感性之间的关系。共招募了82名MG患者和82名健康对照者，使用SNaPshot技术对lncRNA突变热点snp进行基因分型。采用实时荧光定量PCR检测34例MG患者和37例健康对照者的lncRNA表达情况。结果：在多步计算中，MG中3个lncRNAs （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患者与对照组的基因型和等位基因频率无统计学差异。然而，在lncRNA AL031686.1中，rs1000383和rs6094353处于完全连锁不平衡（LD）状态，并与眼部MG风险增加相关。此外，rs6094347与眼部MG风险增加相关。然而，没有发现SNP与性别、年龄、胸腺瘤的存在与否或MG的遗传模式等因素相关。进一步的实验表明，与健康对照组相比，MG患者外周血单个核细胞（PBMCs）中的NONHSAT028539.2表达上调。结论：在我们的研究中，我们没有发现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的rs6094347和rs1000383/rs6094353多态性与眼部MG的风险相关。

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Identification and validation of lncRNA mutation hotspot SNPs associated with myasthenia gravis susceptibility

Background

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.

Methods

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.

Results

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.

Conclusion

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.

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来源期刊

Non-coding RNA Research Medicine-Biochemistry (medical)

CiteScore

7.70

自引率

6.00%

发文量

审稿时长

49 days

期刊介绍： Non-coding RNA Research aims to publish high quality research and review articles on the mechanistic role of non-coding RNAs in all human diseases. This interdisciplinary journal will welcome research dealing with all aspects of non-coding RNAs-their biogenesis, regulation and role in disease progression. The focus of this journal will be to publish translational studies as well as well-designed basic studies with translational and clinical implications. The non-coding RNAs of particular interest will be microRNAs (miRNAs), small interfering RNAs (siRNAs), small nucleolar RNAs (snoRNAs), U-RNAs/small nuclear RNAs (snRNAs), exosomal/extracellular RNAs (exRNAs), Piwi-interacting RNAs (piRNAs) and long non-coding RNAs. Topics of interest will include, but not limited to: -Regulation of non-coding RNAs -Targets and regulatory functions of non-coding RNAs -Epigenetics and non-coding RNAs -Biological functions of non-coding RNAs -Non-coding RNAs as biomarkers -Non-coding RNA-based therapeutics -Prognostic value of non-coding RNAs -Pharmacological studies involving non-coding RNAs -Population based and epidemiological studies -Gene expression / proteomics / computational / pathway analysis-based studies on non-coding RNAs with functional validation -Novel strategies to manipulate non-coding RNAs expression and function -Clinical studies on evaluation of non-coding RNAs The journal will strive to disseminate cutting edge research, showcasing the ever-evolving importance of non-coding RNAs in modern day research and medicine.