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

Genet Test Mol Biomarkers. 2020 Mar;24(3):120-130. doi: 10.1089/gtmb.2019.0193. Epub 2020 Feb 28.


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 the BMPR2 protein. Conclusion: The G allele of MALAT1 gene rs664589 locus SNP is associated with an increased 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.

Keywords: bone morphogenetic protein receptor type 2; hypertension; lung adenocarcinoma metastasis-associated gene 1; single nucleotide polymorphism.

MeSH terms

  • Adenocarcinoma of Lung / genetics
  • Adult
  • Aged
  • Aged, 80 and over
  • Alleles
  • Bone Morphogenetic Protein Receptors, Type II / genetics
  • Cell Line, Tumor
  • China
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Genetic Predisposition to Disease / genetics
  • Genotype
  • Humans
  • Hypertension / genetics*
  • Lung Neoplasms / genetics
  • Male
  • MicroRNAs / genetics
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism


  • MALAT1 long non-coding RNA, human
  • MIRN485 microRNA, human
  • MIRN539 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • BMPR2 protein, human
  • Bone Morphogenetic Protein Receptors, Type II