A Meta-Analysis of the Association between Microrna-196A2 and Risk of Ischemic Stroke and Coronary Artery Disease in Asian Population (original) (raw)
Related papers
Molecular Medicine Reports, 2016
Small non-coding microRNAs (miRNAs) are not only important for heart and vascular development but are also important in cardiovascular pathophysiology and diseases, such as ischemia and atherosclerosis-related diseases. However, the effect of miR-146a, miR-149, miR-196a2 and miR-499 polymorphisms on coronary artery disease (CAD) susceptibility remain unknown. The aim of the present study was to examine the genotype frequencies of miR-146a, miR-149, miR-196a2 and miR-499 polymorphisms in patients with CAD, and assess their clinical applications for diagnosing and monitoring CAD. Using polymerase chain reaction-amplified DNA, microRNA polymorphisms were analyzed in 522 patients with CAD and 535 control subjects. The miR-149 rs2292832 C>T and miR-196a2 rs11614913 T>C polymorphisms were shown to be significantly associated with CAD prevalence. In subgroup analyses according to disease severity, the miR-146a rs2910164GG genotype was significantly associated with CAD risk in the stent ≥2 group. In addition, miR-146aG/-149T/-196a2C/-499 G allele combination was significantly associated with CAD prevalence (G-T-C-G and G-CC -G of miR-146a/-149/-196a2/-499). The combination genotypes of miR-146aGG/149TC+CC and miR-149CC/196a2TC were significantly associated with CAD incidence. In subgroup analyses, miR-146a rs2910164 C>G increased the risk of developing CAD in non-smoking, hypertensive and nondiabetic subgroups. Furthermore, miR-149 rs2292832 C>T and miR-196a2 rs11614913 T>C was shown to increase CAD risk in females and patients aged >63 years old. The miR-149T allele, miR-196a2C allele and miR-146aG/-149T/-196a2C/-499 G allele combination were associated with CAD pathogenesis. The combined effects of environmental factor and genotype combination of miRNA polymorphisms may contribute to CAD prevalence. miRNA polymorphisms (miR-146a, miR-149, miR-196a2 and miR-499) are associated with the risk of coronary artery disease
AIMS: Recent studies have suggested that single-nucleotide polymorphisms (SNPs) in miRNA genes or their binding sites may alter an individual's susceptibility to coronary artery disease (CAD). In the present study, the association between two such SNPs (rs2910164 in miR-146a and rs12190287, which disrupts miRNA binding to TCF21) and CAD, in an Iranian population, was evaluated and in silico analyses were conducted to predict disease-related effects of miR-146a rs2910164. METHODS: The study population consisted of angiographically confirmed CAD patients (n = 300) and asymptomatic controls (n = 300). Genotyping was performed using the TaqMan genotyping assay. RESULTS: A multivariate regression analysis revealed that rs2910164 was associated with an increased CAD risk in the dominant model. In comparison to GG homozygotes, individuals who carry at least one C allele had a significantly higher risk of CAD (GC+CC vs. GG, odds ratios [OR]: 1.82, 95% confidence intervals [CI]: 1.18-2.80, p = 6.358e-3). Similarly, TCF21 rs12190287 was observed to be associated with CAD in a log-additive model (OR: 0.63, 95% CI: 0.45-0.88, p = 6.584e-3). An in silico analysis revealed that rs2910164 may modify the miR-146a-3p-mediated regulation of several biological processes that are implicated in CAD, like those that are related to the regulation of apoptosis and immune response. CONCLUSIONS: Our data provide the first evidence for the association of miR-146a rs2910164 and TCF21 rs12190287 with CAD in an Iranian population, encouraging further research to elucidate the disease-related effects of miR-146a rs2910164.
The Egyptian Journal of Neurology, Psychiatry and Neurosurgery
Background Beside common risk factors for stroke such as diabetes and hypertension, single-nucleotide variants occurring within micro RNA genes have been identified as susceptibility loci for ischemic stroke risk. Objectives Investigate the possible association of two variants in pre miRNA sequences, rs11614913 within miR-196a2 C > T and rs2292832 within miR-149 T > C, with ischemic stroke. Subjects and methods One hundred ischemic stroke patients and 100 age and sex-matched controls having > 1 risk factor for atherosclerosis were enrolled in a case-control study. Degree of atherosclerosis was assessed using ultrasonography. Micro RNA variants were assessed by real-time PCR TaqMan probe assay. Results The TT genotype and T allele frequencies of miR-196a2 C > T were protective against ischemic stroke (OR 0.168, P 0.001; OR 0.482, P < 0.001 respectively). While among miR-149 T > C variants, CC genotype was associated with increased risk by threefold (OR 3.061, P 0.00...
Association of miR-149 (RS2292832) Variant with The Risk of Coronary Artery Disease
Journal of Medical Biochemistry, 2017
SummaryCoronary artery disease (CAD) is the most common cause of mortality and disability from incommunicable disease in the world. Although the association between the single nucleotide polymorphisms (SNPs) in protein-coding genes and the risk of CAD has been investigated extensively, very few heart-disease associated studies concerning the SNPs in miRNA genes have been reported. The present study was performed to elucidate the association between the pre-microRNA-149 (miR-149) SNP rs2292832 and the risk of CAD in an Iranian population.Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) were performed to identify the genotypes of the miR-149 SNP rs2292832 in 421 unrelated subjects (272 with CAD and 149 controls).Our analysis revealed that the TT genotype was more frequent in CAD patients than control subjects (P=0.02) implying that TT genotype should be considered as a risk factor in CAD development (TT vs. TC+CC p=0.02, OR=1.88).The present study su...
Gene, 2015
The microRNA146a rs2910164 polymorphism has been associated with the development of cardio-cerebrovascular diseases (CCDs); however, the results were inconsistent among different studies. The present report was aimed to investigate the association between rs2910164 G/C polymorphism and the risk of CCDs. Based on the data extracted from 12 eligible studies with a total of 5433 CCD cases and 6278 controls, we performed a meta-analysis to assess the diseases risk of rs2910164 G/C polymorphism under allelic contrast (C vs. G), homozygote comparisons (CC vs. GG), heterozygote comparisons (GC vs. GG), dominant model (CC+GC vs. GG) and recessive models (CC vs. GC+GG) in fixed or random effects models. We also conducted pathway enrichment analyses using the putative and validated miR-146a interacting targets to explore the functional impacts of rs2910164. The current meta-analysis results showed that rs2910164 CC genotype has a decreased risk with overall cardiovascular diseases and the spe...
Association of miR-21, miR-126 and miR-605 gene polymorphisms with ischemic stroke risk
Oncotarget, 2017
We investigated whether three common microRNA polymorphisms (miR-21T>C [rs1292037], miR-126G>A [rs4636297] and miR-605T>C [rs2043556]) were associated with ischemic stroke (IS) risk in a Chinese population. The study population comprised 592 ischemic stroke patients and 456 normal controls. The polymorphisms were measured using Snapshot SNP genotyping assays and confirmed by sequencing. Relative expressions of miR-21, miR-126 and miR-605 were measured by quantitative real-time PCR. We found that miR-126 gene rs4636297 polymorphism was associated with decreased ischemic stroke risk (GA vs. GG: AOR=0.64, adjust P=0.025; AA vs. GG: AOR=0.32, adjust P=0.007; dominant model: AOR=0.58, adjust P=0.004). MiR-21 gene rs1292037 and miR-605 gene rs2043556 polymorphisms were not associated with ischemic stroke risk. In addition, compared with normal controls, serum miR-126 level was significantly decreased in ischemic stroke patients, while the miR-21 level was significantly increased....
miRNA polymorphisms and risk of premature coronary artery disease
Hellenic Journal of Cardiology, 2020
This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Mutagenesis, 2012
MicroRNAs (miRNAs) are small non-coding RNA molecules, which act as post-transcriptional regulators of gene expression and have been implicated in initiation, progression and treatment outcome of diverse cancers. Single nucleotide polymorphisms (SNPs), as the most common type of genetic variation, also exist in miRNA genes and can lead to alteration in miRNA expression resulting in diverse functional consequences. Emerging studies have evaluated the association of miRNA SNPs with cancer risk, but the results remain inconclusive. To assess the relationship between miRNA SNPs and cancer risk, we performed a meta-analysis of 18 studies involving 20 660 subjects for miR-146a rs2910164 polymorphism and 21 studies involving 26,018 subjects for miR-196a2 rs11614913 polymorphism. As for rs2910164, no significant association of cancer risk was found in the overall analysis. In subgroup analysis by cancer type, ethnicity, source of controls and sample size, significant association of cancer risk was mainly found in papillary thyroid carcinoma, primary liver cancer, cervical cancer, Caucasian population and small sample size studies. For rs11614913, significant results were found in all the tested genetic models and T allele or its carriers were associated with decreased cancer risk in overall analysis (T vs. C: OR = 0.888, 95% CI 0.84-0.938; TT+TC vs. CC: OR = 0.897, 95% CI 0.828-0.971). In stratified analysis by cancer type and ethnicity, significant association of cancer risk was observed in breast cancer, lung cancer, colorectal cancer and Asian population, but not in Caucasian population. During further stratified analysis by source of controls and sample size, results similar to those of overall analysis were found in all of the subgroups. Taken together, our results indicated that miR-196a2 rs11614913 T variant probably contribute to decreased susceptibility to cancer. However, limited evidence was found for association of miR-146a rs2910164 with cancer risk, and further well-designed studies with large sample size will be necessary to validate the effect of miR-146a rs2910164 on cancer susceptibility.
MicroRNA Expression Profile in CAD Patients and the Impact of ACEI/ARB
Cardiology research and practice, 2011
Coronary artery disease (CAD) is the largest killer of males and females in the United States. There is a need to develop innovative diagnostic markers for this disease. MicroRNAs (miRNAs) are a class of noncoding RNAs that posttranscriptionally regulate the expression of genes involved in important cellular processes, and we hypothesized that the miRNA expression profile would be altered in whole blood samples of patients with CAD. We performed a microarray analysis on RNA from the blood of 5 male subjects with CAD and 5 healthy subjects (mean age 53 years). Subsequently, we performed qRT-PCR analysis of miRNA expression in whole blood of another 10 patients with CAD and 15 healthy subjects. We identified 11 miRNAs that were significantly downregulated in CAD subjects (P < .05). Furthermore, we found an association between ACEI/ARB use and downregulation of several miRNAs that was independent of the presence of significant CAD. In conclusion, we have identified a distinct miRNA ...
Association Between Coronary Artery Disease and MicroRNA: Literature Review and Clinical Perspective
Cureus, 2017
Background Until recently, circulating micro-RNAs (miRNAs) have attracted major interest as novel biomarkers for the early diagnosis of coronary artery disease (CAD). This review article summarizes the available evidence on the correlation of micro-RNAs with both the clinical and subclinical coronary artery disease and highlights the necessity for exploring miRNAs as a potential diagnostic and prognostic biomarker of early CAD in an adult population. Methods A systematic literature analysis and retrieval online systems Public/Publisher MEDLINE/ Excerpta Medica Database /Medical Literature Analysis and Retrieval System Online, (PUBMED/EMBASE/MEDLINE) search were conducted for relevant information. Search was limited to the articles published in English language and conducted on humans, January 2000 onwards. We excluded studies of heart surgery, coronary artery bypass grafting (CABG), angioplasty and heart transplant. Eighteen studies met the inclusion criteria. Results Seven out of 18 studies were multivariate, i.e. adjusted for age, gender, body mass index (BMI), smoking, hypertension, diabetes, and blood lipid profiles, while the remaining twelve studies were univariate analysis. Different sources of miRNAs were used, i.e. plasma/serum, microparticles, whole blood, platelets, blood mononuclear intimal and endothelial progenitor cells were investigated. Fourteen out of 18 studies showed up-regulation of different miRNA in CAD patients and in vulnerable plaque disease. Four out of 18 studies showed both the upregulation and down-regulation of miRNA in the population, while only three studies showed down-regulation of miRNA. Various sources and types of miRNA were used in each study. Conclusion 1 2