MALAT1 gene rs600231 polymorphism positively associated with acute coronary syndrome in Chinese population: a case-control study

Abstract

Background: Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been recognized as a major player in the pathogenesis of coronary artery disease (CAD). The aim of the study was to determine the association between polymorphisms of the MALAT1 gene and acute coronary syndrome (ACS) in a Chinese population in Xinjiang.Methods: In the case-control study, we genotyped three nucleotide polymorphisms (rs3200401, rs4102217, rs600231) of the MALAT1 gene using SNPscan TM typing assays (1,053 controls and 929 ACS patients).Furthermore, we explored a predictive model using MALAT1 rs600231 and clinical variables to predict the risk of ACS. Finally, the relative expression of long noncoding RNA (lncRNA) MALAT1 was also measured in 92 ACS patients and 92 controls using quantitative real-time polymerase chain reaction (qRT-PCR).Results: The prevalence of the GG genotype of rs600231 in ACS group was higher than that in control group (15.7% vs. 14.7%, P=0.048). The dominant model differed (AG + GG vs. AA) and the G allele of rs600231 in ACS group was higher than that in control group (for dominant model: 66.2% vs. 60.9%, P=0.014; for allele: 41.0% vs. 37.8%, P=0.042). Multivariate logistic regression analysis and the predictive nomogram model showed that the dominant model of rs600231 remained an independent risk factor for ACS [odds ratio (OR) =1.32, 95% confidence interval (CI): 1.07-1.63, P=0.009]. The area under the receiver operating characteristic (ROC) curve (AUC) for the nomogram model for the prediction of ACS was 0.738 (95% CI: 0.716-0.761). In addition, in the AG and GG phenotypes, the relative expression of lncRNA MALAT1 was significantly higher in ACS patients than in controls with the same phenotypes (P<0.05).Among ACS group, compared to other genotype carriers, the relative expression level of MALAT1 in GG genotype carriers was higher (P<0.05). Conclusions:The present study suggested that the AG and GG genotype of rs600231 in MALAT1 gene was independently associated with ACS, and could be a risk genetic marker of ACS in a Chinese population in Xinjiang.

Potential Involvement of LncRNAs in Cardiometabolic Diseases

“…To this end, re-analysis of published GWAS studies and their data sets is important to further identify lncRNAs in disease-suspected loci. As exemplified by ANRIL, there are several polymorphisms in lncRNA genes associated with CAD [62,63], including growth arrest specific 5 (GAS5) [64], H19 [65][66][67], HOX transcript antisense RNA (HOTAIR) [68], metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) [69][70][71], and tumor protein p53 pathway corepressor 1 (TP53COR1, also known as lincRNA-p21) [72]. According to the latest annotation provided by the Ensembl database [73] (https://www.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000251562;r=11:65497688-65506516; accessed on 11 January 2023), there are 17 transcripts (isoforms) of MALAT1.…”