Student Research Committee, Babol University of Medical Sciences, Babol, Iran.
Department of Medical Genetics, School of Medicine, Babol University of Medical Sciences, Babol, Iran.
Mol Neurobiol. 2024 May;61(5):2854-2865. doi: 10.1007/s12035-023-03708-x. Epub 2023 Nov 9.
Research findings show that genetic susceptibility to sporadic Parkinson's disease (PD), a common neurodegenerative disorder, is determined through gene variation of loci involved in its development and pathogenesis. A growing body of strong evidence has revealed that dysfunction of long non-coding RNAs (lncRNAs) plays key roles in the pathogenesis and progression of PD through impairing neuronal signaling pathways, but little is known about the relationship between their variants and PD susceptibility. In this research, we intended to study the relationship between functional SNPs rs12826786C>T, rs3200401C>T, and rs6931097G>A in the key lncRNAs stimulating neuroapoptosis and neuroinflammation in PD, including HOTAIR, MALAT1, and lincRNA-P21, respectively, with susceptibility to PD as well as its clinical symptoms.The population of this study consisted of 240 individuals, including 120 controls and 120 cases, and the sample taken from them was peripheral blood. Genotyping of the target SNPs was done using PCR-RFLP. We found that the healthy individuals carry more T allele of MALAT1-rs3200401C>T compared to the patients (P= 0.019). Furthermore, it was observed that in the dominant genetic model, subjects with genotypes carrying the T allele have a lower risk of PD (OR= 0.530; CI= 0.296-0.950; P= 0.033). Regarding the lincRNA-P21-rs6931097G>A, we observed a significant protective relationship between its GA (OR= 0.144; CI= 0.030-0.680; P= 0.014) and AA (OR= 0.195; CI= 00.047-0.799; P= 0.023) genotypes with the manifestation of tremor and bradykinesia symptoms, respectively. Furthermore, the findings indicated that the minor TT genotype of HOTAIR-rs12826786C>T was significantly associated with a reduced risk of bradykinesia symptoms (OR= 0.147; CI= 0.039-0.555; P= 0.005). Collectively, these findings suggest that MALAT1-rs3200401C>T may be an important lncRNA SNP against the development of PD, while the other two SNPs show protective effects on the clinical manifestations of PD in a way that lincRNA-P21-rs6931097G>A has a protective effect against the occurrence of tremor and bradykinesia symptoms in PD patients, and HOTAIR -rs12826786C>T indicates a protective effect against the display of bradykinesia feature. Therefore, they can have valuable potential as biomarkers for clinical evaluations of this disease.
研究结果表明，散发性帕金森病（PD）这一常见神经退行性疾病的遗传易感性是由涉及疾病发展和发病机制的基因座的基因变异决定的。越来越多的有力证据表明，长非编码 RNA（lncRNA）的功能障碍通过损害神经元信号通路在 PD 的发病机制和进展中发挥关键作用，但它们的变体与 PD 易感性之间的关系知之甚少。在这项研究中，我们旨在研究关键 lncRNA 刺激神经细胞凋亡和神经炎症的功能 SNP rs12826786C>T、rs3200401C>T 和 rs6931097G>A 与 PD 易感性及其临床症状的关系。该研究的人群包括 240 名个体，其中 120 名对照和 120 名病例，样本取自外周血。使用 PCR-RFLP 对目标 SNP 进行基因分型。我们发现与患者相比，健康个体携带更多的 MALAT1-rs3200401C>T 的 T 等位基因（P=0.019）。此外，观察到在显性遗传模型中，携带 T 等位基因的基因型个体患 PD 的风险较低（OR=0.530；CI=0.296-0.950；P=0.033）。关于 lincRNA-P21-rs6931097G>A，我们观察到其 GA（OR=0.144；CI=0.030-0.680；P=0.014）和 AA（OR=0.195；CI=0.047-0.799；P=0.023）基因型与震颤和运动迟缓症状的表现之间存在显著的保护关系。此外，研究结果表明，HOTAIR-rs12826786C>T 的 TT 基因型显著降低了运动迟缓症状的风险（OR=0.147；CI=0.039-0.555；P=0.005）。总的来说，这些发现表明 MALAT1-rs3200401C>T 可能是对抗 PD 发展的重要 lncRNA SNP，而其他两个 SNP 对 PD 的临床表现具有保护作用，即 lincRNA-P21-rs6931097G>A 对 PD 患者震颤和运动迟缓症状的发生具有保护作用，而 HOTAIR-rs12826786C>T 对运动迟缓特征的显示具有保护作用。因此，它们可能具有作为该疾病临床评估的有价值的潜在生物标志物。
