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Functional polymorphism of lncRNA MALAT1 contributes to pulmonary arterial hypertension susceptibility in Chinese people.

Abstract：

BACKGROUND:The long noncoding RNAs (lncRNAs) have gradually been reported to be an important class of RNAs with pivotal roles in regulation of gene expression, and thus are involved in multitudinous human complex diseases. However, the biological functions and precise mechanisms of the majority of lncRNAs are still poorly understood. METHODS:In the study, we tested genomic variations in lncRNA-metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) loci, and their potentially functional correlationship with pulmonary arterial hypertension (PAH) susceptibility based on a case-control study with a total of 587 PAH patients and 736 healthy controls in southern Chinese. RESULTS:We found that the rs619586A>G single nucleotide polymorphism (SNP) was significantly associated with PAH risk. The carriers with G variant genotypes had a decreased risk of PAH (odds ratio [OR]=0.69, 95% confidence interval [CI]=0.53-0.90, p=0.007) compared to the rs619586AA genotype. Further functional experiments indicated that the alteration from rs619586A to G in MALAT1 could directly upregulate X box-binding protein 1 (XBP1) expression via functioning as the competing endogenous RNA (ceRNA) for miR-214, and consequentially inhibiting the vascular endothelial cells proliferation and migration in vitro by shortening S-M phase transition. CONCLUSIONS:Taken together, our findings propose that functional polymorphism rs619586A>G in MALAT1 gene plays an important role in PAH pathogenesis and may serve as a potential indicator for PAH susceptibility.

journal_name

Clin Chem Lab Med

journal_title

Clinical chemistry and laboratory medicine

authors

Zhuo Y,Zeng Q,Zhang P,Li G,Xie Q,Cheng Y

doi

10.1515/cclm-2016-0056

subject

Has Abstract

pub_date

2017-01-01 00:00:00

pages

38-46

issue

1

eissn

1434-6621

issn

1437-4331

pii

/j/cclm.ahead-of-print/cclm-2016-0056/cclm-2016-00

journal_volume

55

pub_type

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