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Correlation Between Single Nucleotide Polymorphisms of the rs664589 Locus in the Long-Chain Noncoding RNA Lung Adenocarcinoma Metastasis-Associated Gene 1, Hypertension, and Its Mechanism.
Genetic Testing and Molecular Biomarkers ( IF 1.1 ) Pub Date : 2020-02-28 , DOI: 10.1089/gtmb.2019.0193
Xianyu Mou 1 , Jinglin Wang 1 , Lei Wang 1 , Shumin Wang 1
Affiliation  

Objective: Hypertension is a disease caused by both genetic and environmental factors. In the present study, we analyzed the association of the lung cancer adenocarcinoma metastasis-associated gene 1 (MALAT1) gene rs664589 locus single nucleotide polymorphism (SNP) with the risk of essential hypertension and explored its possible mechanisms. Materials and Methods: We analyzed the genotype of the MALAT1 gene rs664589 locus in 260 hypertensive patients and 260 healthy controls. The levels of plasma long-chain noncoding RNA (lncRNA) MALAT1, hsa-miR-539-3p, and hsa-miR-485-3p were determined by reverse transcription real-time quantitative PCR (qRT-PCR). The effects of MALAT1 on the expression levels of hsa-miR-539-3p, hsa-miR-485-3p, and bone morphogenetic protein receptor type 2 (BMPR2) were detected by transfection of human umbilical vein endothelial cells. Results: The risk of hypertension in subjects carrying the G allele of the MALAT1 gene rs664589 locus was 1.33 times higher than the C allele carriers (95% confidence interval [CI]: 1.15-1.51, p < 0.001). This MALAT1 gene rs664589 locus SNP was significantly associated with the risk of hypertension only in men, subjects with obesity, a history of smoking, and a history of drinking (p < 0.05). lncRNA MALAT1 was downregulated in the plasma of hypertensive patients. In addition, the level of plasma lncRNA MALAT1 was significantly lower in the G allele carriers of the MALAT1 gene than in the C allele carriers (p < 0.001). The lncRNA MALAT1 inhibited the expression of hsa-miR-539-3p and hsa-miR-485-3p and promoted the expression of BMPR2 protein. Conclusion: The MALAT1 gene rs664589 locus SNP is associated with the risk of hypertension. In subjects carrying the G allele, the expression of lncRNA MALAT1 in plasma is significantly decreased, resulting in an abnormally high expression of hsa-miR-539-3p and hsa-miR-485-3p, and inhibition of BMPR2 expression, which might be associated with hypertension; however, further studies in animal models are needed to confirm this hypothesis.

中文翻译:

长链非编码RNA肺腺癌转移相关基因1,高血压的rs664589基因座的单核苷酸多态性与机制的关系。

目的:高血压是由遗传和环境因素引起的疾病。在本研究中,我们分析了肺癌腺癌转移相关基因1(MALAT1)基因rs664589基因座单核苷酸多态性(SNP)与原发性高血压风险的关系,并探讨了其可能的机制。材料和方法:我们分析了260名高血压患者和260名健康对照者的MALAT1基因rs664589基因座的基因型。通过逆转录实时定量PCR(qRT-PCR)确定血浆长链非编码RNA(lncRNA)MALAT1,hsa-miR-539-3p和hsa-miR-485-3p的水平。MALAT1对hsa-miR-539-3p,hsa-miR-485-3p,通过转染人脐静脉内皮细胞来检测骨形态发生蛋白受体2(BMPR2)的表达。结果:携带MALAT1基因rs664589基因座G等位基因的受试者患高血压的危险比C等位基因携带者高1.33倍(95%置信区间[CI]:1.15-1.51,p <0.001)。该MALAT1基因rs664589基因座SNP仅与男性,肥胖,有吸烟史和饮酒史的高血压风险显着相关(p <0.05)。高血压患者血浆中lncRNA MALAT1被下调。另外,血浆lncRNA MALAT1的水平在MALAT1基因的G等位基因携带者中显着低于C等位基因携带者(p <0.001)。lncRNA MALAT1抑制hsa-miR-539-3p和hsa-miR-485-3p的表达,并促进BMPR2蛋白的表达。结论:MALAT1基因rs664589位点SNP与高血压风险有关。在携带G等位基因的受试者中,血浆中lncRNA MALAT1的表达显着降低,导致hsa-miR-539-3p和hsa-miR-485-3p异常高表达,并可能抑制BMPR2表达。与高血压有关;但是,需要在动物模型中进行进一步研究以证实这一假设。导致hsa-miR-539-3p和hsa-miR-485-3p异常高表达,并抑制BMPR2表达,这可能与高血压有关;但是,需要在动物模型中进行进一步研究以证实这一假设。导致hsa-miR-539-3p和hsa-miR-485-3p异常高表达,并抑制BMPR2表达,这可能与高血压有关;但是,需要在动物模型中进行进一步研究以证实这一假设。
更新日期:2020-02-28
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