Long noncoding RNA MALAT1 polymorphism predicts MACCEs in patients with myocardial infarction.

BACKGROUND: Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) participates in the occurrence and development of cardiovascular and cerebrovascular diseases such as stroke and coronary heart disease by regulating inflammatory reactions, programmed cell death, and other pathological processes. Previous studies revealed that the MALAT1 gene polymorphism was associated with cardiac and cerebrovascular diseases. However, the prognostic role of the MALAT1 polymorphism in major adverse cardiac and cerebrovascular events (MACCEs) remains unknown. Therefore, this study intends to explore the association between the MALAT1 rs3200401 polymorphism and MACCEs. METHOD: We enrolled 617 myocardial infarction (MI) patients and 1125 control participants who attended the First Affiliated Hospital of Xinjiang Medical University from January 2010 to 2018. SNPscan™ typing assays were used to detect the MALAT1 rs3200401 genotype. During the follow-up, MACCEs were recorded. Kaplan-Meier curves and univariate and multivariate Cox survival analyses were used to explore the correlation between MALAT1 gene polymorphisms and the occurrence of MACCEs. RESULTS: Among the total participants and MI patients, the frequencies of the T allele (total Participants 19.5% vs. 15.3%, P = 0.047, MI patients 20.7% vs. 14.1%, P = 0.014) and CT + TT genotypes (total Participants 37.4% vs. 28.1%, P = 0.013, MI patients 39.5% vs. 25.8%, P = 0.003) were significantly higher in subjects with MACCEs than in subjects without MACCEs. However, in control participants, the frequencies of the T allele (16.6% vs. 16.0%, P = 0.860) and CT + TT genotypes (31.4% vs. 29.3%, P = 0.760) were not higher in subjects with MACCEs than in subjects without MACCEs. In addition, among the total participants and MI patients, the Kaplan-Meier curve analysis indicated that the subjects with rs3200401 CT + TT genotypes had a higher incidence of MACCEs than CC genotype carriers (P = 0.015, P = 0.001). Nevertheless, similar results were not observed in the control participants (P = 0.790). Multivariate Cox regression indicated that compared with patients with the CC genotype, patients with CT + TT genotypes had a 1.554-fold increase in MACCE risk (hazard ratio: 1.554, 95% confidence interval: 1.060-2.277, P = 0.024). CONCLUSIONS: The MALAT1 rs3200401 CT + TT genotypes could be a risk factor for MACCEs in MI patients, suggesting that the MALAT1 gene may become a biomarker for poor prognosis in MI patients.

Association analysis of MALAT1 polymorphisms and risk of psoriasis among Iranian patients.

MALAT1 is a long non-coding transcript that affects immune reactions, thus being involved in the pathoaetiology of immune-related conditions. We investigated the associations between two genetic variants in MALAT1 and susceptibility to psoriasis in the Iranian population. The G allele of rs619586 has been shown to be less common among cases versus controls (odds ratios (OR; 95% confidence intervals (CI)) = 0.57 (0.36-0.9)), adjusted p = .02). This single nucleotide polymorphism has been associated with the risk of psoriasis in a dominant model (AG + GG vs. AA: OR (95% CI) = 0.56 (0.35-0.92), adjusted p = .04) as well as log-additive model (OR (95% CI) = 0.59 (0.38-0.92), adjusted p = .04). The rs3200401 was not associated with psoriasis in any of the supposed inheritance models. This study potentiates rs619586 as a risk locus for psoriasis in the Iranian population.

The Relationship between MALAT1 Polymorphism rs3200401 C > T and the Risk of Overall Cancer: A Meta-Analysis.

Background and Objectives: At present, the association between the long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) polymorphism rs3200401 C > T and cancer risk remain controversial. The aim of this meta-analysis was to assess the association between rs3200401 C > T and cancer susceptibility. Materials and Methods: The databases of PubMed, EMBASE and Web of Science were searched for literature published in English until 1 September 2021. The odd ratios (ORs) and 95% confidence intervals (CIs) were applied to evaluate the strength of association in five genetic models. Heterogeneity was assessed using the Q-test and I2 test. Begg's funnel plot and Egger's linear regression test were conducted to assess publication bias. Meta-regression analysis was used to explore potential sources of heterogeneity. Trial sequential analysis (TSA) was performed to validate the reliability of the results. Results: A total of 10 case-control studies involving 6630 cases and 7457 controls were included in this study. The pooled ORs showed no significant association between MALAT1 rs3200401 C > T and cancer risk in five genetic models. Similarly, the association was not found in the subgroups of control source, ethnicity and study quality. In the cancer type subgroup, the results demonstrated that the T allele increased the risk of colorectal cancer (CRC) compared with the C allele. (C vs. T: OR, 1.16; 95% CI, 1.01-1.33). Conclusion: In the current meta-analysis, we found no significant association between MALAT1 polymorphism rs3200401 C > T and overall cancer risk. However, the rs3200401 C > T may be linked to a higher risk of CRC, which needs more studies to be further confirmed.

The Role of Genetic Variants in the Long Non-Coding RNA Genes MALAT1 and H19 in the Pathogenesis of Childhood Obesity.

Long non-coding RNAs (lncRNAs) play important roles in the maintenance of metabolic homeostasis. Recently, many studies have suggested that lncRNAs, such as Metastasis Associated Lung Adenocarcinoma Transcript 1 (MALAT1) and Imprinted Maternally Expressed Transcript (H19), might participate in the pathogenesis of metabolic disorders such as obesity. We conducted a case-control study with 150 Russian children and adolescents aged between 5 and 17 years old in order to assess the statistical association between the single nucleotide polymorphisms (SNPs) rs3200401 in MALAT1 and rs217727 in H19, and the risk of developing obesity in this population. We further explored the possible association of rs3200401 and rs217727 with BMI Z-score and insulin resistance. The MALAT1 rs3200401 and H19 rs217727 SNPs were genotyped using Taqman SNP genotyping assay. The MALAT1 rs3200401 SNP was identified as a risk factor for childhood obesity (p < 0.05) under the dominant and allelic models, and the CT heterozygous genotype was associated with the risk of increased BMI and with insulin resistance. The H19 rs217727 SNP had no significant association with obesity risk (all p > 0.05). Our findings thus suggest that MALAT1 SNP rs3200401 is a potential indicator of obesity susceptibility and pathogenesis in children and adolescents.

The contribution of MALAT1 gene rs3200401 and MEG3 gene rs7158663 to the risk of lung, colorectal, gastric and liver cancer.

Previous studies have repeatedly investigated the effects of MALAT1 gene rs3200401 and MEG3 gene rs7158663 on cancer risk. However, their results remain conflicting rather than conclusive. Therefore, we here performed a case-control study and a followed meta-analysis to examine their contribution to the risk of lung, colorectal, gastric and liver cancer. 550 lung cancer patients, 787 colorectal cancer patients, 460 gastric cancer patients, 480 liver cancer patients and 800 normal controls were included. The genotyping of rs3200401 and rs7158663 was applied with Sanger sequencing technology. Our case-control study revealed that in Hubei Chinese population, rs3200401 was significantly associated with the risk of gastric cancer but not lung, colorectal, or liver cancer, rs7158663 was significantly associated with the risk of gastric and colorectal cancer but not lung or liver cancer. The followed meta-analysis, combining the data of previous studies and present study, showed that rs3200401 was significantly associated with the risk of gastric and colorectal cancer in the pooled population but not liver cancer in Chinese population, rs7158663 was significantly associated with the risk of lung, colorectal and gastric but not liver cancer in Chinese population. Collectively, MALAT1 gene rs3200401 may be a susceptive factor for the development of colorectal and gastric cancer, and MEG3 gene rs7158663 may be a susceptive factor for the development of lung, colorectal and gastric cancer. However, the findings should be validated in future studies with larger sample sizes of different ethnic populations.

Long non-coding RNA polymorphisms and prediction of response to chemotherapy based on irinotecan in patients with metastatic colorectal cancer.

BACKGROUND: Colorectal cancer is the fourth cause of cancer related death. Drug resistance and toxicity remain major clinical issues. HOTAIR and MALAT1 are long non-coding RNAS that affect cellular proliferation, apoptosis and drug resistance; their up-regulation has been linked with a poor prognosis. OBJECTIVE: Investigation of the association between rs4759314 HOTAIR and rs3200401 MALAT1 polymorphisms and irinotecan-based chemotherapy in terms of drug efficacy and toxicity. METHODS: Samples from 98 patients receiving different regimens of irinotecan-based therapy were included. Efficacy and toxicity were evaluated. KRAS mutation, rs3200401 HOTAIR and rs4759314 MALAT1 polymorphisms genotyping in the tumors and peripheral blood respectively were performed with PCR. RESULTS: Neither rs3200401 MALAT1 nor rs4759314 HOTAIR polymorphism are associated with response to treatment regimens. Rs4759314 was also not associated with increased toxicity in patients receiving irinotecan-based regimens. CT genotype of rs3200401 was associated with significantly reduced overall survival. An association between KRAS mutation and AG/GG genotypes in the rs4759314 was detected. CONCLUSIONS: CT genotype of rs3200401 MALAT1 polymorphism could serve as a toxicity biomarker. Carriers of the G allele of the rs4759314 HOTAIR are more likely to be carriers of KRAS mutations too. However, further studies in larger patient populations are required.