miR-146a Rs2910164 Research Articles

Association of miR-146a rs57095329 with Behçet’s disease and its complications

ABSTRACT Background Behçet’s disease is a chronic relapsing and remitting autoimmune multisystem inflammatory disease characterised by oral aphthae, genital ulcers, skin lesions, gastrointestinal involvement, arthritis, vascular lesions and neurological manifestations. We hypothesised a link between rs57095329 of miR-146a and Behçet’s disease, with further links with common clinical features. Methods We tested our hypothesis in 130 Behçet’s disease patients and 131 age and sex-matched healthy controls. Behcet’s disease current activity index (BDCAI) was used to assess patients’ disease activity status. MiR-146a (rs57095329) was genotyped in all participants using RT-PCR and results in patients analysed according to clinical features. Results The frequency of the GG and AG genotypes in rs57095329 were strongly associated with Behçet’s disease (adjusted OR 8.05, 95% CI 3.63–17.82; P < 0.001 and OR 2.26, 95% CI 1.27–4.04; P = 0.006, respectively), and in dominant (GG+AG > AA) and recessive (GG > AA+AG) models (both P < 0.001). Additionally, G allele distribution was significantly greater in Behçet’s disease compared with controls (OR 2.85, 95% CI 1.98–4.11, P < 0.001). The AA genotype and A allele were linked to oral ulcers, the GG genotype and G allele to neurological disease, and the GG genotype and G allele to ocular disease (all P < 0.01). There were no links with genital ulceration, skin lesions, vascular disease or the result of the pathergy test. Conclusion The miR-146a (rs57095329) is associated with Behçet’s disease and certain genotypes and alleles with oral ulcers, and with ocular and neurological manifestations.

The association of miR-27a rs895819 polymorphism with colorectal cancer risk in Chinese population.

BackgroundBesides environment and living habits, such as a sedentary lifestyle, smoking and drinking, genetic variation also plays an important role in the development of colorectal cancer (CRC). This study was aimed to investigate the role of miR‑27a rs895819 polymorphism on CRC risk in Chinese population.MethodsIn a case‐control study including 208 CRC and 312 age‐ and gender‐matched healthy control subjects, the rs895819 polymorphism was genotyped using the TaqMan allelic discrimination assay. Furthermore, a pooled analysis based on eligible studies was performed by using the STATA software.ResultsLogistic regression analysis showed that the rs895819 polymorphism was not associated with CRC risk. However, a pooled analysis based on five studies from Chinese population showed a statistically significant association between the rs895819 polymorphism and CRC risk (GG vs AA: OR = 1.56, 95% CI = 1.27‐1.92, Pz < .01; (AG + GG) vs AA: OR = 1.14, 95% CI = 1.01‐1.30, Pz = .04; GG vs (AG + AA): OR = 1.54, 95% CI = 1.27‐1.88, Pz < .01; G vs A: OR = 1.20, 95% CI = 1.09‐1.33, Pz < .01).ConclusionOur study suggests that miR‑27a rs895819 polymorphism plays an important role in CRC risk in Chinese population and may serve as a valuable biomarker for predicting an individual's susceptibility to CRC.

Association of miR-27a polymorphism with the risk of digestive system cancers

BackgroundCancer of the digestive system is a common cancer and results in high mortality rates world-wide. miR-27a polymorphism has been associated with an increased risk of digestive system cancers; however, this has not been conclusively shown yet. Therefore, to clarify this, we conducted a comprehensive meta-analysis. MethodsPubMed, EMBASE, OVID and Cochrane Library databases were comprehensively searched to retrieve eligible studies published up to May 10, 2020 that referred to digestive cancers. Odds ratios and the corresponding 95 % confidence intervals (CI) were used when calculating the relationship between miR-27a rs895819 polymorphism and susceptibility to digestive cancers. ResultsA significant correlation between the miR-27a rs895819 polymorphism and the presence of digestive system cancers was found in four genetic models, which were the homozygote, dominant, recessive, and allele genetic models (GG vs AA: OR = 1.210, 95 %CI = 1.020–1.436, P = 0.029; GG + AG vs AA: OR = 1.092, 95 %CI = 1.024–1.164, P = 0.007; GG vs AG + AA: OR = 1.182, 95 %CI = 1.005–1.390, P = 0.044; G vs A: OR = 1.099, 95 %CI = 1.046–1.154, P < 0.001). Hierarchical analysis by ethnicity suggested that miR-27a rs895819 significantly increased the risk of digestive system cancers in the Asian population, but not in Caucasians. Additionally, rs895819 polymorphism was found to be significantly associated with colorectal cancer and gastric cancer. ConclusionsThe miR-27a rs895819 polymorphism may be associated with an increased risk for digestive system cancers.

Multiple sclerosis: an associated single-nucleotide polymorphism study on Egyptian population

Multiple Sclerosis (MS) is an autoimmune disease that severely impacts the central nervous system. Thanks to the evolutionary genetic information studied and published, researches have started to study MS from a genetic perspective. This paper provides a study of six single-nucleotide polymorphisms (SNPs)—MIR137HG (rs1625579), GAS5 (rs2067079), MIR3142HG (rs57095329), MIR146A (rs2910164), MIR155HG (rs767649) and IRAK1 (rs3027898)—and demonstrates their association with MS. This study was applied over an Egyptian dataset of 38 MS patients and 35 controls. Hence, different models were applied, Dominant, Recessive and Genotypic models along with Fisher’s Exact method, Basic case–control analysis and Logistic regression analysis. This paper shows that the SNPs rs1625579, rs57095329, rs767649 and rs3027898 are associated with MS (p value < 0.05) according to all tested models except for Recessive model, that has add-in the relevance of rs1625579, rs57095329, rs2910164 and rs767649 with MS disease.

Association between miRNA-146a polymorphism and lung cancer susceptibility: A meta-analysis involving 6506 cases and 6576 controls.

We sought to analyze the association between miR-146a rs2910164 G > C polymorphism and susceptibility to lung cancer using a meta-analysis of case-control studies. We systematically searched for studies reporting on the relationship between miR-146a rs2910164 polymorphism and the risk of lung cancer in PubMed, Embase, Web of Science and Chinese National Knowledge Infrastructure databases. We then calculated pooled odds ratios (ORs), at 95% confidence interval (CI) to assess the aforementioned relationship. All the data were analyzed using statistical packages implemented in R version 3.6.2 (R Project for Statistical Computing), run in RStudio version 1.2.5033. A total of fifteen studies, comprising 6506 cases and 6576 controls, were enrolled in this meta-analysis. Significant associations were observed between miR-146a rs2910164 polymorphism and the risk of lung cancer based on overall pooled subjects under the allele, heterozygous, homozygous, dominant, and recessive genetic models (C vs. G: OR = 1.27, 95% CI: 1.12-1.44; GC vs. GG: OR = 1.23, 95% CI: 1.03-1.46; CC vs. GG: OR = 1.51, 95% CI: 1.18-1.93; GC + CC vs. GG: OR = 1.33, 95% CI: 1.10-1.61; CC vs. GG + GC: OR = 1.32, 95% CI: 1.13-1.53). Ethnicity-based subgroup analyses revealed no statistically significant differences in Asians using heterozygous and dominant genetic models. miR-146a rs2910164 G > C polymorphism may be a risk factor of lung cancer. Asian populations exhibiting heterozygous and dominant genotypes need to be further investigated to validate our findings.

Investigation of the Association between a Genetic Variant in MiR-196a-2 Gene and the Risk of Lung Cancer in the Iranian Population

Introduction: MicroRNAs (miRNAs) play an important role in the expression of their target genes. The single-nucleotide polymorphisms (SNPs) in miRNAs may affect their function and expression. The aim of the present study was to investigate the association between miR-196a2 rs116614913 polymorphism and non-small cell lung cancer (NSCLC) in the Iranian population.Materials and Methods: This case-control study was performed among 103 lung cancer patients and 100 healthy controls. The polymerase chain-reaction restriction fragment length polymorphism (PCR-RFLP) method and direct sequencing were used for miR-196a2 polymorphism genotyping. Statistical analyses were performed using SPSS software and t test method.Results: According to the findings of this study, there was no significant association between rs11614913 polymorphisms and the risk of lung cancer in codominant model (CT vs. CC: OR = 0.67, TT vs. CC: OR = 0.74, CT + CC vs. CC: OR = 1.133), dominant model (CT+TT vs. CC: OR=0.657) and recessive model (TT vs. CC+CT: OR = 0.88). In addition, there was no relationship between the clinicopathological characteristics of patients and controls.Conclusions: In summary, findings indicated no significant association between miR-196a2 rs11614913 polymorphisms and lung cancer in the Iranian population. Further studies with larger sample sizes are recommended to verify these findings.

A SNP of miR-146a is involved in bladder cancer relapse by affecting the function of bladder cancer stem cells via the miR-146a signallings.

MiR‐146a‐5p in urine samples was recently reported to be possibly used as a prognostic marker for bladder cancer (BC). Interestingly, YAP1 and COX2 were both demonstrated to function as stem cell regulators in BC. Therefore, in this study, we aimed to establish the molecular mechanism underlying the role of miR‐146a, YAP1 and COX2 in BC relapse. We also studied the possibility of using the C > G genotype of miR‐146a rs2910164 SNP as an indicator of BC relapse. A total of 170 BC patients were assigned into different groups based on their genotypes of rs2910164 SNP. Kaplan‐Meier survival curves were plotted to compare the recurrence‐free rate among these groups. Real‐time PCR, Western Blot, bioinformatic analysis, luciferase assay and IHC assay were conducted to study the role of rs2910164 SNP in the progression of BC. Accordingly, GC/CC‐genotyped patients presented a higher risk of recurrence when compared with GG‐genotyped patients, while the expression of BC regulators was influenced by the presence of rs2910164. COX2 mRNA and YAP1 mRNA were, respectively, validated as direct target genes of miR‐146a, and the expression of YAP1 and COX2 mRNA/protein was both suppressed by miR‐146a precursors. The expression of ALDH1A1 mRNA/protein was inhibited upon the down‐regulation of YAP1, while the expression of let7 and SOX2 mRNA/protein was inhibited upon the down‐regulation of COX2. In conclusion, two signalling pathways, miR‐146a/YAP1/ALDH1A1 and miR‐146a/COX2/PGE2/let7/SOX2, were modulated by miR‐146a. As an SNP regulating the expression of miR‐146a, the rs2910164 G > C SNP could be utilized as a biomarker for BC relapse.

Correlations of miR-146a and IRAK1 gene polymorphisms with ankylosing spondylitis.

The aim of this study was to explore the correlations of micro ribonucleic acid (miR)-146a and interleukin 1 receptor associated kinase 1 (IRAK1) gene polymorphisms with ankylosing spondylitis. A total of 200 patients with ankylosing spondylitis in our hospital were enrolled in the disease group. The diagnosis of ankylosing spondylitis was in accordance with the 1984 New York Revised Criteria for Ankylosing Spondylitis. Meanwhile, 200 healthy people were taken as the control group. Peripheral blood was collected from patients in both disease group and control group. Subsequently, polymorphic regions of rs2910164 and rs7702165 in miR-146a and those of rs763737 and rs3027898 in IRAK1 were amplified by polymerase chain reaction (PCR). The polymorphisms were analyzed by sequencing based on gene expression and clinical data of patients. The allele distribution of miR-146a rs7702165 (p=0.008) and that of IRAK1 rs3027898 (p=0.004) in disease group were significantly different from those in control group. Besides, the allele T frequency of miR-146a rs7702165 and the allele A frequency of IRAK1 rs3027898 were relatively higher in disease group. Statistically significant differences in the genotype distribution of miR-146a rs2910164 (p=0.032) and rs7702165 (p=0.000) and that of IRAK1 rs3027898 (p=0.001) were observed between disease group and control group. In addition, the frequencies of genotypes CG and TT of miR-146a rs7702165 and the frequency of genotype AA of IRAK1 rs3027898 were higher in disease group. Moreover, the distribution in the dominant model of IRAK1 rs3027898 (p=0.011) and that in the recessive model of miR-146a rs7702165 (p=0.015) showed remarkable differences between disease group and control group. The frequency of CC+CA in the dominant model of IRAK1 rs3027898 and that of TG+GG in the recessive model of miR-146a rs7702165 in disease group were lower than those in control group. Additionally, the haplotype CG distribution of miR-146a rs2910164 and rs7702165 (p<0.043) and the haplotype GA distribution of IRAK1 rs763737 and rs3027898 (p=0.035) in disease group displayed significant differences compared with those in control group. It was discovered that the genotype of miR-146a rs2910164 was correlated with the expressions of miR-146a (p=0.024) and IRAK1 (p=0.002). Similarly, IRAK1 gene polymorphism rs763737 was related to the expression of IRAK1 (p=0.023), Furthermore, miR-146a gene polymorphism rs7702165 was associated with the level of human leukocyte antigen B27 (HLA-B27) (p<0.05), and patients with genotype GG exhibited a lower level of HLA-B27. In addition, it was found that IRAK1 gene polymorphism rs3027898 was correlated with the C-reactive protein (CRP) level of patients (p<0.05), and CRP level was relatively high in patients with genotype CC. MiR-146a and IRAK1 gene polymorphisms are prominently associated with ankylosing spondylitis.

Association between miR-196a2 polymorphism and the development of hepatocellular carcinoma in the Egyptian population

BackgroundHepatocellular carcinoma (HCC) is one of the most prevalent cancers worldwide. Circulating microRNAs (miRNAs) are endogenous, small (17–25 nucleotides) non-coding RNAs that are overexpressed in many human cancers including HCC. Single-nucleotide polymorphisms (SNPs) of miRNAs play an important role in the pathogenesis of HCC. In our study, we aimed to evaluate the role of miR-196a2 rs11614913 polymorphism in the development of HCC. A total of 200 subjects, including 80 HCC patients, 60 patients with liver cirrhosis, and 60 healthy controls were selected. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was taken to determine miR-196a2 rs11614913 polymorphism.ResultsThe genotype distribution of the TC and CC, TC + CC genotypes, and the C allele were significantly higher in HCC patients than control and cirrhotic groups (P = 0.02, P = 0.005, and P = 0.003, respectively). Compared with the wild-type TT genotype, both the variant TC, CC, TC + CC genotypes were associated with an elevated risk of HCC (OR = 2.77, 95% CI = 1.27–6.04), (OR = 4.94, 95% CI = 1.74–14.07), (OR = 3.24, 95% CI = 1.55–6.78) respectively. Moreover, the C allele was correlated with an increased risk of HCC (OR = 2.30, 95% CI = 1.40–3.76) compared to the wide-type T allele. Also, there is no significant correlation between the different miR-196a2 genotypes and either the clinico-pathologic features of HCC or its aggressiveness.ConclusionOur results suggest that the miR-196a2 rs11614913 polymorphism is associated with an increased risk of HCC in the Egyptian population.

Relationship between miR-155 and miR-146a polymorphisms and susceptibility to multiple sclerosis in an Egyptian cohort.

Multiple sclerosis (MS) is an autoimmune disorder of the central nervous system. It was previously demonstrated that miR-155 and miR-146a served a vital role in the pathophysiology of MS, and single nucleotide polymorphisms in miR-155 and miR-146a were found to be associated with the susceptibility to different autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis and type I diabetes. The aim of the present study was to analyze the association between susceptibility to MS and two genetic polymorphisms (miR-155 rs767649 A>T and miR-146a rs57095329 A>G) in a cohort of Egyptian patients. The presence of the two polymorphisms were analyzed in 114 patients with MS and 152 healthy controls using quantitative PCR. The present study demonstrated for the first time that: The TT genotype and T allele in miR-155 (rs767649 A>T) polymorphism were associated with an increased risk of MS; the miR-146a (rs57095329 A>G) mutated G allele conferred protection against the development of MS in all genetic models; miR-155 rs767649 A>T was a risk associated polymorphism of MS in females, but not in males; and miR-155 rs767649 AT/TT and miR-146a rs57095329 GG genotypes showed significantly higher distributions among patients with higher Expanded Disability Status Scale scores and secondary progressive MS subgroups. Therefore, miR-155 rs767649 polymorphism may confer susceptibility to MS, whereas miR-146a rs57095329 may be protective against MS in an Egyptian cohort.

Association Between the Functional miR-146a SNP rs2910164 and Risk of Digestive System Cancer: Updated Meta-analysis.

Previous association studies have linked the functional miR-146a SNP rs2910164 with risk of digestive system cancer; however, the results of these studies are inconclusive and inconsistent. The objective of the following study is to provide an up-to-date and comprehensive meta-analysis of the association of miR-146a rs2910164 and digestive system cancer risk. We searched the PUBMED/MEDLINE and Cochrane/EBM databases. The following inclusion criteria were used for the study selection: i) Case-control studies; ii) studies with reported allelic frequency/genotype data; and iii) studies with reported association with risk of a digestive system cancer. The following exclusion criteria were used: Review article, meta-analysis, case report and case series; studies evaluating relationships of miR-146a rs2910164 with outcomes other than cancer incidence, such as cancer morbidity or mortality. Study quality was assessed using the Newcastle-Ottawa Scale and publication bias assessed graphically and numerically using Begg's funnel plot and Egger's regression test and rank test. Outcome measure was the pooled odds ratios under the allelic frequency, dominant, recessive, and over-dominant models. Subgroup analysis was conducted for country of study origin. No association of miR-146a rs2910164 with overall risk of digestive system cancer was identified. However, subgroup analysis showed an association with overall risk in the European population in the over-dominant model. Furthermore, miR-146a rs2910164 was associated with reduced risk of gastric cancer in the dominant model (pooled odds ratio=0.91, 95% confidence intervaI=0.83-0.99), increased risk of colorectal cancer under the recessive model and reduced risk of colorectal cancer under the over-dominant model in the European population. No significant within-study or publication biases were detected. miR-146a rs2910164 was not associated with overall risk of digestive system neoplasms. However, the GG genotype and the CC genotype may be linked to higher risk of gastric cancer and colorectal cancer, respectively; and the CG genotype may be protective against digestive system neoplasms overall in the European population, especially for colorectal cancer.

Association between MIR499A rs3746444 polymorphism and breast cancer susceptibility: a meta-analysis

Numerous studies have investigated the association of MIR499A rs3746444 polymorphism with breast cancer susceptibility, but the results have been inconsistent. In this work, we performed a meta-analysis to obtain a more reliable estimate of the association between the polymorphism and susceptibility to breast cancer. A comprehensive literature search was conducted on PubMed, Scopus, Web of Science (WoS), China National Knowledge Infrastructure (CNKI), VIP and Wanfang databases up to January 2020. A total of 14 studies involving 6,797 cases and 8,534 controls were included for analysis under five genetic models: homozygous (GG vs. AA), heterozygous (AG vs. AA), dominant (AG + GG vs. AA), recessive (GG vs. AA + AG) and allele (G vs. A). A statistically significant association was observed between the polymorphism and an increased breast cancer susceptibility under all genetic models (homozygous, OR = 1.33, 95% CI = 1.03–1.71, P = 0.03; heterozygous, OR = 1.08, 95% CI = 1.00–1.16, P = 0.04; dominant, OR = 1.15, 95% CI = 1.02–1.30; P = 0.03; recessive, OR = 1.35, 95% CI = 1.06–1.72, P = 0.01; allele, OR = 1.12, 95% CI = 1.00–1.26, P = 0.04). Subgroup analysis based on ethnicity suggested that significant association was present only among Asians, but not Caucasians. In conclusion, MIR499A rs3746444 polymorphism was significantly associated with breast cancer susceptibility among Asians, suggesting its potential use as a genetic risk marker in this population.

Fas and microRNAs Variations as a Possible Risk for Behçet Disease.

Behçet disease (BD) belongs to a disease family that has a transparent borderline between autoinflammatory and autoimmune disorders. Fas and some miRNAs have revealed to display remarkable roles in both autoimmune and autoinflammatory processes, and they can play important roles in defective apoptosis in BD. We investigated the association of the susceptibility of BD with Fas, miRNA variations, and their both single and combined presence in a Turkish population as a case-control study. The distributions of FAS-670 A>G rs1800682, mir146a rs2910164, and mir196a rs11614913 polymorphisms are analyzed with the polymerase chain reaction-restriction fragment length polymorphism method in 115 BD patients and 220 controls in 6-month period. Statistical analysis indicates that in the case of Fas-670 A/G rs1800682, AA genotype and A allele have a protective role in BD (p = 0.0004 and p = 0.0009, respectively). The dominant model (AA + AG/GG) also displays a protective effect on BD unlike the recessive model (p = 0.03). In addition, both homozygous genotype (CC) of rs2910164 of mir-146a (p = 0.04) and the dominant model (CC + CG vs. GG) have protective effects on BD unlike the recessive model (p < 0.0001). Both mir-196a2 rs1800682 polymorphism and combined genotype analysis of rs1800682-rs2910164 and rs1800682-rs11614913 gave no statistically significant differences within the groups for genotypes and either of the alleles (p > 0.05). These findings indicate that both Fas rs1800682 and mir-146a rs2910164 variants might be important factors participating in the protection against BD in the Turkish population.

Association between polymorphisms in microRNA seed region and warfarin stable dose

BackgroundThe optimal dose of anticoagulant warfarin varies among patients to achieve the target international normalised ratio. Although genetic variations related to warfarin pharmacokinetics and vitamin K cycle are important factors...

Significant Association Between the MiR146a Genotypes and Susceptibility to Childhood Acute Lymphoblastic Leukemia in Taiwan.

Mounting evidence has shown that miRNAs play a critical role in the regulation of hematopoiesis of cell proliferation and apoptosis as well as in tumorigenesis. The miR146a rs2910164 polymorphism, which is closely responsive for its expression, has been reported to associate with the risk of several solid cancers. The study aimed at examining the association of the it with susceptibility to childhood acute lymphoblastic leukemia (ALL) in Taiwan. We recruited 266 patients with childhood ALL and 266 healthy controls, and rs2910164 genotypes were determined by the polymerase chain reaction-restriction fragment length polymorphism methodology. The allele G was associated with decreased childhood ALL risk (OR=0.66, 95%CI=0.52-0.85, p=0.0011). Consistently, the GG genotype was associated with a decreased susceptibility (OR=0.40, 95%CI=0.23-0.67, p=0.0004). Patients with CG and GG genotypes were of earlier onset than those with CC genotype (p=0.0255 and p=0.0001). MiR146a rs2910164 G allele serves as a protective marker for childhood ALL in Taiwan.

Nuclear factor-κB1 and MicroRNA-146a polymorphisms and risk of acute graft versus host disease post allogeneic stem cell transplantation.

Acute graft-versus-host disease (aGVHD) is a severe inflammatory complication of haematopoeitic stem cell transplantation. The nuclear factor- Kappa Beta (NF-κB) signaling pathway regulates T cell activation. The NF-κB controls the expression of microRNA-146a (miR-146a) that in turn regulates NF-κB activation through a negative feedback loop. We aim to analyze the association between NF-κB1 encoding p50 (rs28362491, -94 in.ertion/deletion ATTG) and miR-146a (rs2910164, G > C) polymorphisms and risk of aGVHD. Genotyping was performed for 135 HLA-matched donors using polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP).The incidence of aGVHD grades II-IV was 24/135 (17.8 %). NF-κB1 genotype and cytomegalovirus infection were significantly associated with risk of aGVHD II-IV (p = 0.022, HR = 3.17, 95 % CI:1.18-8.51 and p = 0.048, HR = 2.56, 95 % CI:1.01-6.52, respectively). In multivariate analysis, NF-κB1homozygous deletion/deletion genotype was the only independent risk factor associated with aGVHD II-IV (p = 0.013, HR = 3.50, 95 % CI:1.30-9.44). No significant association could be observed between miR-146a polymorphism and aGVHD. Combined NF-κB1 and miR146a genotype analysis warrants investigation in a larger cohort. Our preliminary data do not support the association between miR146a and aGVHD, but suggest an association between NF-κB1 and risk of aGVHD that may pave the way for the development of a novel targeted therapy if proved in a larger cohort.

Association of microRNA-146a rs2910164 polymorphism with type II diabetes mellitus in a South Indian population and a meta-analysis

Type 2 diabetes mellitus (T2DM) is a metabolic disorder caused by impaired insulin secretion and/or insulin resistance. Ever since its discovery, microRNAs have been studied for their implication in several human diseases. Recently many studies have reported the role of certain microRNAs in the development of T2DM. Mir-146a is a negative regulator of interleukin-1 receptor-associated kinase 1 (IRAK-1) and tumour necrosis factor receptor-associated factor 6 (TRAF-6) proteins and is known to play an important role in inflammation, innate immunity, beta-cell differentiation and insulin resistance. Here we aimed to investigate the association of mir-146a SNP rs2910164 with the risk of T2DM in an Indian population and a meta-analysis of existing literature on the same. We recruited 100 diabetic and 100 -non-diabetic subjects for the study. Blood samples, clinical and anthropometric parameters were collected. The rs2910164 SNP was genotyped using PCR-RFLP. A comprehensive literature survey was done on the role of mir-146a rs2910164 and meta-analysis was performed on the available eligible studies including the current study. The case-control study showed that the CC genotype and C allele was associated with an increased risk of T2DM. There was no significant association between the genotypes and biological parameters. The meta-analysis showed that the polymorphism was not associated with T2DM significantly. In conclusion, mir-146a rs2910164 plays a role as a risk factor in T2DM but the results need to be warranted with further studies.

Associations Between microRNA Polymorphisms and Development of Coronary Artery Disease: A Case-Control Study.

Coronary artery disease (CAD), a common cardiovascular disease, has become a vital cause of mortality worldwide. Genetic microRNA (miR) polymorphisms might contribute to CAD susceptibility. In this study, we selected miR-146a, miR-196a2, and miR-499 single nucleotide polymorphisms and conducted a case-control study. In total, 505 CAD cases and 1109 controls were recruited. We used SNPscan™ genotyping assay to obtain genotyping of miR rs2910164, rs11614913, and rs3746444 variants. We found that miR-196a2 rs11614913 T > C decreased the susceptibility of myocardial infarction (MI) (TC vs. TT: adjusted p = 0.007 and CC/TC vs. TT: adjusted p = 0.012). In female subgroup, our results indicated that miR-196a2 rs11614913 T > C variants might also decrease the susceptibility of CAD (TC vs. TT: adjusted p = 0.017 and TC/CC vs. TT: adjusted p = 0.015). In summary, these results suggest that miR-196a2 rs11614913 T > C locus decreases the susceptibility of CAD in female and MI subgroups. However, further studies are needed to validate the potential associations of miR-196a2 rs11614913 locus with CAD.

APRISMA-compliant systematic review and meta-analysis determining the association of miRNA polymorphisms and risk of congenital heart disease.

Purpose:Recent genetic association studies showed conflicting results on the relationship of miRNA single-nucleotide polymorphisms (SNPs) and congenital heart disease (CHD) risk. The purpose of the present systematic review was to collect the current available evidences to evaluate the association between miRNA polymorphisms and CHD risk.Methods:Four electronic databases including PubMed, EMBASE, ISI Web of Science, and CENTRAL were extensively searched for relevant studies published before February, 2019. Observational studies determining the association between miRNA polymorphisms and risk of CHD were included. Risk of bias was evaluated using the Newcastle-Ottawa Scale by 2 independent researchers. Major characteristics of each study and estimation of effect size of individual locus polymorphism were summarized. In addition, meta-analysis was performed to quantify the associations between miRNA polymorphisms and CHD risk.Results:Nine studies containing 6502 CHD patients and 6969 healthy controls were included in this systematic review. Ten loci in 9 miRNAs were reported. Only rs11614913 in miR-196a2 was determined to have significant associations with CHD susceptibility, which was supported by meta-analysis (CC vs CT+TT: odds ratio 1.54, 95% confidence interval 1.30, 1.82; P < .00001). A strong evidence indicated lack of association between rs2910164 in miR-146a and CHD. Limited or conflicting evidences were found for the associations of the other variants (rs11134527, rs139365823, rs76987351, rs3746444, rs4938723, rs2292832, rs41291957, rs895819) and risk of CHD.Conclusions:Locus polymorphisms in miRNAs are not generally associated with CHD. Only rs11614913 was found to have significant associations with CHD. Further studies will be needed, using larger populations of different ethnicities, to obtain a better understanding of these associations.

Association between polymorphisms in microRNAs and susceptibility to diabetes mellitus: A meta-analysis.

Background:Accumulated evidence has indicated the associations between single-nucleotide polymorphisms (SNPs) in microRNAs (miRNAs) and the susceptibility to diabetes mellitus (DM), but the conclusions remain controversial. This study was to investigate the true contribution of miRNA SNPs to the risk of DM by using a meta-analysis of all the published studies.Methods:Relevant studies were identified in the databases of PubMed and the Cochrane Library databases. The strength of associations between miRNA polymorphisms and DM risk was assessed by odds ratios (ORs) and 95% confidence intervals (95% CIs) under five genetic models using the STATA software.Results:Six studies, containing 2773 cases and 2632 controls, were enrolled, 5 of which evaluated miR-146a (rs2910164), 4 for miR-27a (rs895819), and 3 for miR-124 (rs531564) and 2 for miR-375 (rs6715345), miR-128a (rs11888095), miR-194a (rs3820455). The meta-analysis indicated that the G allele or GG genotype of miR-146a rs2910164 was associated with a significantly increased risk for DM compared with C allele or GC/CC genotype in Latin American population; CC genotype of miR-27a rs895819 polymorphism was associated with a significantly decreased risk for DM in Asian population compared with the TT genotype; patients carrying with CC genotype of miR-124 rs531564 had a lower probability to develop DM regardless of ethnicity; no associations were identified between polymorphisms in miR-375, miR-128a, miR-194a and the susceptibility to DM.Conclusion:Our study suggests that miR-146a/miR-27a and miR-124 polymorphisms may be ethnicity-dependent or -independent susceptibility factors to DM, respectively.