miR-146a Polymorphisms Research Articles

Type 1 diabetes mellitus and its genetic association with miR-146a and miR-155 single nucleotide polymorphisms (SNPs)

Back groundThe current case- control study investigated, the relation of miRNA146a (rs2910164) and miRNA 155 (rs767649) single nucleotide polymorphisms (SNPs), and the incidence of T1DM in a sample of Pediatric Egyptian patients. Patients and methodsOne hundred and twenty-two patients diagnosed with type 1DM, were enrolled in the study. One hundred and two sex matched healthy subjects of the same ethnic were taken as a control group. Through history taking, clinical and physical examination, and anthropometric measurements were done to all participating patients. Polymerase chain reaction-restriction fragment length poly-morphism (PCR –RFLP) technique was performed for amplifying and genotyping of miRNA-146a (rs2910164). Genotyping of miR-155 (T/A) (rs767649) was performed using TaqMan allelic discrimination technique (RT-PCR). ResultsThe minor C allele of miRNA 146a was significantly higher in the control group compared to the diabetic group under the co-dominant (p = 0.009, p = 0.005; respectively), dominant (p = 0.001) and additive genetic models (p = 0.003). The interaction between the miRNA 146a and miRNA 155 SNPs, revealed that the prevalence of DM tends to be lower if minor alleles were inherited by the subject (p = 0.04, p = 0.003; respectively). ConclusionThe study, provides evidence suggesting that miRNA146a SNP may have a protective role against the incidence of T1DM. The inheritance of minor alleles of miRNA 146a and/or miRNA 155 were more prevalent within the healthy control group in comparison to the patient's group which implies that both SNPs may interact to confer protection against T1DM.

Assessment of Association between miR-146a Polymorphisms and Expression of miR-146a, TRAF-6, and IRAK-1 Genes in Patients with Brucellosis

Brucellosis is a major zoonosis all over the world. MicroRNAs are significant gene expression regulators and could be involved during the infections and also genetic alterations in the miRNAs sequence can affect primary miRNAs and precursor miRNAs processing and thus alter miRNAs expression. Current research studied the impact of the miR-146a polymorphism on miR-146a, TRAF-6, and IRAK-1 genes expression in patients with brucellosis illness. In this research, 25 patients with brucellosis and 25 healthy participants with determined genotypes for miR-SNP rs2910164 and miR-SNP rs57095329 were recruited. IRAK-1, TRAF-6, and miR-146a expressions in peripheral blood mononuclear cells (PBMCs) were specified by quantitative real- time PCR (qRT-PCR). Moreover, interleukin-1β (IL-1β) and tumor necrosis factor- alpha (TNF-α) serum levels were assessed by a sandwich enzyme-linked immunosorbent assay (ELISA) technique. There was no significant difference in the expression level of miR-146a, IRAK-1, and TRAF-6, among the patients with brucellosis and control group. TRAF-6 PBMCs expression levels in the distinctive genotypes of rs2910164 were significantly observed in patients (P = 0.048). No significant distinctions were found in miR-146a, IRAK-1, and TRAF-6 expression levels and among the rs57095329 different genotypes in brucellosis patients and controls. Meanwhile, no significant relationship was found between the rs2910164 and rs57095329 genotypes and the serum level of cytokines mentioned between the two groups. We did not find any association between expression of TRAF-6, miR-146a, and IRAK-1 in PBMCs, and cytokines serum levels with two single nucleotide polymorphisms (SNPs) in miR-146a. To the best of writers' knowledge, this research is the first one evaluating the probable link between the miR-146a rs2910164 and rs57095329 variant with miRNAs, relevant cytokine levels, and target genes in brucellosis.

Association of four gene polymorphisms in Chinese Guangxi population with diabetic retinopathy in type 2 diabetic patients

sBackgroundDiabetic retinopathy (DR) is one of the most common chronic microvascular complications of diabetes. Many studies have suggested that genetic factors are important in the context of DR. This study evaluated the associations of GWAS (Genome-wide association study) -identified DR-associated SNPs in a Chinese population in Guangxi Province with type 2 diabetes mellitus (T2DM).MethodsA total of 386 hospitalized T2DM patients without proliferative diabetic retinopathy (PDR) and 316 hospitalized T2DM patients with PDR were included in this case–control study. Four tag SNPs, including rs1800896 in the IL-10 gene, rs2010963 in the VEGFA gene, rs2070600 in the RAGE gene and rs2910164 in the miR-146a gene, were examined using KASP (kompetitive allele specific PCR) genotyping assays.ResultsThere were no significant differences in the genotype or allele frequencies of the miR-146a polymorphism (rs2910164) between subjects with PDR and those without DR. The TC genotype of rs1800896 was determined to be associated with an increased risk of PDR (the odds ratio (OR) was 2.366, with a 95% confidence interval (CI) ranging from 1.144 to 4.894). The CG genotypes of rs2010963 was associated with an decreased risk of PDR (the OR was 0.588, with a 95% CI ranging from 0.366 to 0.946). Regarding rs2070600, 2 genotypes (TT and CT) were associated with a decreased risk of PDR (the OR of the TT genotype was 0.180, with a 95% CI ranging from 0.037 to 0.872, and the OR of the CT genotype was 0.448, with a 95% CI ranging from 0.266 to 0.753).ConclusionsThe rs1800896 polymorphisms in the IL-10 gene, rs2010963 in the VEGFA gene and rs2070600 in the RAGE gene are associated with the risk of PDR in the Han Chinese population of Guangxi Province. Our findings provide suggestive evidence that these polymorphisms may be involved in the pathogenesis of PDR and should be investigated further.

Meta-Analysis of miRNA Variants Associated with Susceptibility to Autoimmune Disease.

Purpose Various studies have shown an association between miRNA polymorphisms and susceptibility to autoimmune disease (AD); however, the results are inconclusive. To evaluate whether miRNA polymorphisms account for a significant risk of AD, a total of 87 articles, including 39431 patients and 56708 controls, were identified to estimate their association with 12 AD subtypes. Methods Several electronic databases were searched to analyze population-based studies on the relationship between miRNA variants and AD risk. Fixed effects or random effect models were used in the meta-analysis for the risk assessment. Results In our meta-analysis, miR-146a rs2910164/rs57095329 conferred a marginally elevated risk for AD (allele model, OR = 1.08, 95% CI: 1.01-1.15, P = 0.019; allele model, OR = 1.09, 95 CI: 1.05-1.15, P < 0.001, respectively). Furthermore, miR-196a2 rs11614913 was also associated with AD risk (allele model, OR = 0.92, 95% CI: 0.88-0.97, P = 0.001) as well as miR-499 rs3746444 (allele model, OR = 1.16, 95% CI: 1.03-1.29, P = 0.011). In addition, associations were observed between miR-149 rs2292832/miR-27a rs895819 and AD susceptibility in the overall population (allele model, OR = 1.15, 95% CI: 1.06-1.24, P < 0.001; allele model, OR = 1.11, 95% CI:1.01-1.22, P = 0.043, respectively). Conclusions Evidence from our systematic review suggests that miR-146a, miR-196a2, miR-499, miR-149, and miR-27a polymorphisms are associated with susceptibility to AD.

Relation between Mir-196a2 and Mir-146a Polymorphisms and Susceptibility to DM1 in Egyptian Children

Relation between Mir-196a2 and Mir-146a Polymorphisms and Susceptibility to DM1 in Egyptian Children

MicroRNA-146a and its target gene IRAK1 polymorphisms confer susceptibility to systemic lupus erythematosus

ObjectiveTo clarify the association between miR-146a, miR-499, and IRAK1 polymorphism and systemic lupus erythematosus (SLE) predisposition. MethodsA literature search was conducted until 12 September 2020 in accordance with the PRISMA guidelines. The keywords “miRNA-146a”, “miRNA-499”, “IRAK1” and “SLE” were used in combination to obtain case-control studies evaluating the abovementioned gene polymorphism and the risk of SLE. ResultsPatients harbouring C allele of miRNA-146a rs2431697 exhibited low SLE risk (CC vs. TC+TT, OR=.77, 95% CI=.62–.95, p=.019; TC vs. CC+TT, OR=.84, 95% CI=.71–.98, p=.027; and TC vs. TT, OR=.73, 95% CI=.61–.86, p=.000), whereas patients carrying the A allele and AA genotype of rs3027898 in IRAK1 had significantly decreased SLE susceptibility (A vs. C, OR=.73, 95% CI=.60–.87, p=.001; AA vs. CA+CC, OR=.64, 95% CI=.42–.97, p=.037; AA+CA vs. CC, OR=.71, 95% CI=.56–.88, p=.003, and AA vs. CC, OR=.49, 95% CI=.31–.77, p=.002). No association was observed between miRNA-146a rs2910164 and miRNA-499 rs3746444 with SLE risk. ConclusionThis study demonstrates associations between miRNA-146a and IRAK1 polymorphisms with SLE risk. Larger studies on these associations are needed in the future to support our results.

Association of miR-146a and miR-499 polymorphisms with susceptibility to rheumatoid arthritis: a Meta-analysis

Association of miR-146a and miR-499 polymorphisms with susceptibility to rheumatoid arthritis: a Meta-analysis

Serum Levels of miR-146a in Patients with Psoriasis.

Psoriasis is an immune-mediated disease with interactions between genetic and environmental factors. An increasing number of studies are demonstrating the importance of microRNAs (miRNAs) in the pathogenesis of psoriasis. miR-146a, a dominant negative regulator of inflammation, has been consistently reported as overexpressed in the skin and peripheral blood mononuclear cells (PBMCs) of patients with psoriasis. Expression and/or function of this miRNA is highly influenced by genetic variations, some of which have already been associated with susceptibility to psoriasis. We sought to study the importance of miR-146a in patients with moderate-to-severe psoriasis and to understand the impact of rs57095329 and rs2910164 polymorphisms in a psoriatic Portuguese population. miR-146a circulating levels were quantified using molecular biology techniques in 99 patients with moderate-to-severe psoriasis (35 female, 64 male; age 47.4 ± 10.9 years) and 78 healthy individuals (52 female, 26 male; age 42.4 ± 10.1 years). miRNA expression was correlated with clinicopathological features as well as with genetic data such as the presence of human leukocyte antigen (HLA)-C*0602 allele and two miR-146a polymorphisms (rs2910164 and rs57095329). miR-146a serum levels were 3.7-fold higher in patients with psoriasis than in controls (p < 0.0001, area under the curve [AUC] 0.75; 95% confidence interval [CI] 0.66-0.83). Of note, miR-146a circulating levels positively correlated with Psoriasis Area and Severity Index (p < 0.05) and body surface area (p < 0.05) indexes. No variations in miR-146a levels were observed with rs2910164 and rs57095329 genotypes. Circulating miR-146a levels were upregulated in patients with psoriasis, especially in those with active disease. To the best of our knowledge, this is the largest study with a homogenous psoriasis population, and our data could shed light on the pathogenesis of psoriasis, paving the way for new avenues for disease treatment.

MiR-146a and miR-155 polymorphisms in Egyptian patients with Behcet's disease.

The current study was designed to analyze whether polymorphisms of miR-146a and miR-155 are related to Behçet's disease (BD) in the Egyptian population. A total of 96 unrelated BD patients and 100 healthy subjects were genotyped for miR-146a (rs2910164) and miR-155 (rs767649) using real-time polymerase chain reaction. The results showed significant elevation in the frequency of rs2910164 GG and CC genotypes in BD patients compared with controls (adjusted OR = 22.156, 95% CI: 4.728-103.818; p < 0.001 and adjusted OR = 40.358, 95% CI: 8.928-182.440; p < 0.001, respectively). Also, the rs2910164 G allele conferred a higher risk of developing BD (adjusted OR = 3.665, 95% CI: 2.013-6.671; p < 0.001). MiR-146a (rs2910164) polymorphism was a risk factor for susceptibility to BD in dominant, recessive and additive models of inheritance (all p < 0.001), while the miR-155 (rs767649) polymorphism was a risk factor in the recessive model only (p = 0.021). GG and CG genotypes of rs2910164 were associated with higher Behcet's disease current activity index (BDCAI) and ocular involvement compared with CC genotype (p = 0.005 and p = 0.004, respectively). Genotype AT of rs767649 was related to higher BDCAI (p = 0.026) compared with TT and AA genotypes. miR-146a (rs2910164) and miR-155 (rs767649) are likely to play an important role in the Egyptian population in development of BD and also influence disease severity.

MiR-146a in Cardiovascular Diseases and Sepsis: An Additional Burden in the Inflammatory Balance?

The new concept of thrombosis associated with an inflammatory process is called thromboinflammation. Indeed, both thrombosis and inflammation interplay one with the other in a feed forward manner amplifying the whole process. This pathological reaction in response to a wide variety of sterile or non-sterile stimuli eventually causes acute organ damage. In this context, neutrophils, mainly involved in eliminating pathogens as an early barrier to infection, form neutrophil extracellular traps (NETs) that are antimicrobial structures responsible of deleterious side effects such as thrombotic complications. Although NETosis mechanisms are being unraveled, there are still many regulatory elements that have to be discovered. Micro-ribonucleic acids (miRNAs) are important modulators of gene expression implicated in human pathophysiology almost two decades ago. Among the different miRNAs implicated in inflammation, miR-146a is of special interest because: (1) it regulates among others, Toll-like receptors/nuclear factor-κB axis which is of paramount importance in inflammatory processes, (2) it regulates the formation of NETs by modifying their aging phenotype, and (3) it has expression levels that may decrease among individuals up to 50%, controlled in part by the presence of several polymorphisms. In this article, we will review the main characteristics of miR-146a biology. In addition, we will detail how miR-146a is implicated in the development of two paradigmatic diseases in which thrombosis and inflammation interact, cardiovascular diseases and sepsis, and their association with the presence of miR-146a polymorphisms and the use of miR-146a as a marker of cardiovascular diseases and sepsis.

The Polymorphism of miR-146a (rs2910164) and Breast Cancer Risk: A Meta-Analysis of 17 Studies.

Single-Nucleotide Polymorphisms (SNPs) in genes responsible for coding microRNAs (miRNAs) are shown to be crucial in progression of Breast Cancer (BC). The purpose of this meta-analysis is to obtain more definitive and reliable results due to the ambiguity and inconsistency of the previous findings in this regard. This study aimed at clarifying the association of mir14a polymorphisms with breast cancer. We searched PubMed, EMBASE, Web of Science and Google Scholar databases for papers published before August 10, 2019. Afterward, genotypes' distribution, genotyping methods and ethnicity groups were extracted and Overall analyses were conducted. A total number of seventeen researches on 7676 subjects and 7476 controls were found to meet our criteria in this meta-analysis. Our observations confirmed the increased risk in breast cancer with rs 2910164 polymorphism in three genetic models: allele contrast fixed genetic model, Recessive fixed genetic model and CC vs. GG genetic model (P value 0.0109, 0.0404 and 0.0019, respectively). The rs2910164 polymorphism is associated with increased breast cancer risk. We suggest that more multicenter studies with larger samples investigate this matter to further clarify the association and verify our findings.

Impact of miR-155 (rs767649 A>T) and miR-146a (rs57095329 A>G) polymorphisms in System Lupus Erythematosus susceptibility in an Egyptian cohort.

Systemic Lupus Erythematosus (SLE) is an autoimmune inflammatory disease. miR-155 and miR-146a were expressed in many autoimmune diseases such as rheumatoid arthritis. The aim of this study was to examine miR-155 rs767649 and miR-146a rs57095329 polymorphisms in SLE susceptibility in an Egyptian cohort and to investigate the correlation between them and clinical data and disease activity. The two SNPs were analyzed in 120 patients with SLE and 100 healthy controls using RT-PCR. The TT genotype and T allele of miR-155 rs767649 were associated with a significant increase in the risk of SLE, particularly in females. On the other hand, miR-146a (rs57095329) polymorphism was not associated with SLE risk. The AT/TT genotypes of miR-155 rs767649 showed higher distributions among patients with higher SLEDAI and nephritis. This study had demonstrated for the first time the association between miR-155 rs767649 and the risk of development of SLE in an Egyptian cohort, mostly in females.

MicroRNA-146a switches microglial phenotypes to resist the pathological processes and cognitive degradation of Alzheimer's disease.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease and currently has no effective treatment. Mainstream research on the mechanisms and therapeutic targets of AD is focused on the two most important hallmarks, Aβ and Tau, but the results from clinical studies are not encouraging. Abnormal microglial polarization is a clear typical pathological feature in the progression of AD. Microglia can be neuroprotective by degrading and removing Aβ and Tau. However, under AD conditions, microglia transform into a pro-inflammatory phenotype that decreases the phagocytic activity of microglia, damages neurons and promotes the pathology of AD. We previously reported that a miR-146a polymorphism is associated with sporadic AD risk, and the nasal administration of miR-146a mimics reduced cognitive impairment and the main pathological features of AD. However, it is not clear by what mechanism miR-146a resists the pathological process of AD. In this study, we discovered that microglia-specific miR-146a overexpression reduced cognitive deficits in learning and memory, attenuated neuroinflammation, reduced Aβ levels, ameliorated plaque-associated neuritic pathology, and prevented neuronal loss in APP/PS1 transgenic mice. In addition, we found that miR-146a switched the microglial phenotype, reduced pro-inflammatory cytokines and enhanced phagocytic function to protect neurons in vitro and in vivo. Moreover, transcriptional analysis confirmed that miR-146a opposed the pathological process of AD mainly through neuroinflammation-related pathways. In summary, our results provide sufficient evidence for the mechanism by which miR-146a opposes AD and strengthen the conclusion that miR-146a is a promising target for AD and other microglia-related diseases.

An association study between MiR-146a and INSR gene polymorphisms and hypertensive disorders of pregnancy in Northeastern Han Chinese population

IntroductionHypertensive disorders of pregnancy(HDP) is a complex and challenging group of pregnancy complications that is one of the leading causes of maternal and fetal death worldwide. Recent studies have shown that the single nucleotide polymorphism(SNP) may play a role in the pathogenesis of HDP. This study aimed to investigate the association of MiR-146a rs2910164 and insulin receptor(INSR) rs2059806 SNPs with HDP and their associated complications in the Han population of Northeast China. MethodsA total of 240 HDP patients and 380 healthy controls were selected for genotype determination. For the most special and high incidence of HDP, we also studied the SNPs in association with pre-eclampsia(PE) patients. In addition, HDP complicated with gestational diabetes mellitus(GDM) patients was further analyzed to identify the association between SNPs and HDP-related complications. Multivariate logical regression analysis combined with 10, 000 permutation test corrections was used to analyze the association of MiR-146a and INSR SNPs with HDP. ResultsAfter adjusting for relevant factors, MiR-146a rs2910164 or INSR rs2059806 SNPs were not significantly different between HDP or PE patients and healthy controls(P>0.05). Meanwhile, MiR146a rs2910164 and INSR rs2059806 SNPs were not significantly different between HDP complicated with GDM and control group. DiscussionOur data indicates that MiR-146a rs2910164 and INSR rs2059806 SNPs may not be significantly related with HDP in the Han population of Northeast China living in Heilongjiang Province.

Association of miR-146α gene polymorphism and expression levels of its target protein RhoA in Pakistani breast cancer patients.

To assess the association of miR-146a and its target protein RhoA expression levels in breast cancer. The case-control study was conducted at Riphah International University, Islamabad, Pakistan, from March 2017 to November 2018, and comprised confirmed breast cancer cases and controls who were matched for age and ethnicity. Genotyping and expression profiling of archived samples was performed. Data was analysed using SPSS 22. Of the 590 subjects, 295(50%) each were cases and controls. Among the cases, there were 195(66%) Punjabis, 59(20%) Pathans and 41(14%) Kashmiris. The corresponding numbers among the controls were 198(67%), 58(19.7%) and 39(13.2%). The association between genotypes of the cases and controls was significant (p<0.05). Strong association was seen in dominant, recessive and allelic models (p=0.05). In Punjabi group the association was (p<0.00) significant, but this association was not significant in Kashmiri and Pathan groups (p>0.05). No association was found with the receptor status and miR-146a polymorphism. The miR-146a gene polymorphism rs2910164 G/C was found to have increased susceptibility to breast cancer at genotype and allelic levels.

Relationship analysis of the miR-196a2 polymorphism (rs11614913) with colorectal cancer risk in southern Khorasan, eastern Iran

BackgroundIt has been considered that colorectal cancer (CRC) is the fourth most common cause of cancer death with multifactorial characteristics and genetic precedent can provide a comprehensive sight to its etiology. Single nucleotide polymorphisms (SNPs) in microRNAs (miRNAs /miRs) sequence are considered as prognostic markers with high specify for CRC detection and prevention. Recent researches have indicated that rs11614913 is the most common SNP related to the vulnerability to many of the cancers. This case-control study aims to quantify the correlation between rs11614913 in miR-196a2 and CRC in southeast Iranian population. MethodsTo identify the role of rs11614913 SNP in susceptibility to CRC, this case-control study is done on CRC patients (n = 52) and healthy persons (n = 120) of the same organization with a uniform gender and age dispensation compared to CRC patients and no prior background of any kind of cancer by PCR-RFLP technique. Statistical analysis is carried out utilizing SPSS (version 16). ResultsAfter the comparison of genotype and allele distribution of this SNP among case and control groups, it has not shown any statistically significant findings (P > 0.05). ConclusionWe have not discovered statistically significant association between rs11614913 polymorphism in miR-196a2 and the risk of CRC in the southeast Iranian society.

The influence of genetic variability in IL1B and MIR146A on the risk of pleural plaques and malignant mesothelioma.

BackgroundAsbestos exposure is associated with the development of pleural plaques as well as malignant mesothelioma (MM). Asbestos fibres activate macrophages, leading to the release of inflammatory mediators including interleukin 1 beta (IL-1β). The expression of IL-1β may be influenced by genetic variability of IL1B gene or regulatory microRNAs (miRNAs). This study investigated the effect of polymorphisms in IL1B and MIR146A genes on the risk of developing pleural plaques and MM.Subjects and methodsIn total, 394 patients with pleural plaques, 277 patients with MM, and 175 healthy control subjects were genotyped for IL1B and MIR146A polymorphisms. Logistic regression was used in statistical analysis.ResultsWe found no association between MIR146A and IL1B genotypes, and the risk of pleural plaques. MIR146A rs2910164 was significantly associated with a decreased risk of MM (OR = 0.31, 95% CI = 0.13–0.73, p = 0.008). Carriers of two polymorphic alleles had a lower risk of developing MM, even after adjustment for gender and age (OR = 0.34, 95% CI = 0.14–0.85, p = 0.020). Among patients with known asbestos exposure, carriers of at least one polymorphic IL1B rs1143623 allele also had a lower risk of MM in multivariable analysis (OR = 0.50, 95% CI = 0.28–0.92, p = 0.025). The interaction between IL1B rs1143623 and IL1B rs1071676 was significantly associated with an increased risk of MM (p = 0.050).ConclusionsOur findings suggest that genetic variability of inflammatory mediator IL-1β could contribute to the risk of developing MM, but not pleural plaques.

MiR-146a rs2910164 G\u2009>\u2009C polymorphism modulates Notch-1/IL-6 signaling during infection: a possible risk factor for Crohn\u2019s disease

BackgroundMiR-146a, an effector mediator, targets Notch-1 and regulates the innate and adaptive immune systems response. Recently, we reported that Notch-1 signaling plays a key role in macrophage polarization and response during infection. We employed Mycobacterium avium paratuberculosis (MAP) infection in Crohn’s disease (CD) as a model to demonstrate the role of Notch-1/IL-6 signaling on MCL-1 based apoptosis and intracellular MAP infection and persistence. This study was designed to investigate the impact of polymorphisms in miR146a on the immune response and infection in our MAP-CD model.MethodsWe determined the incidence of miR-146a rs2910164 G > C in 42 blood samples from clinical CD patients and controls. We also measured the effect of rs2910164 on expression of Notch-1 and IL-6, and plasma IL-6 protein levels in our study group. Finally, we analyzed the blood samples for MAP DNA and studied any correlation with miR-146a polymorphism. Samples were analyzed for statistical significance using unpaired tow-tailed t-test, unpaired two-tailed z-score and odds ratio. P < 0.05 considered significant.ResultsMiR-146a rs2910164 GC was detected at a higher incidence in CD (52.6%) compared to healthy controls (21.7%) rs2910164 GC Heterozygous polymorphism upregulated Notch-1 and IL-6, by 0.9 and 1.7-fold, respectively. As expected, MAP infection was detected more in CD samples (63%) compared to healthy controls (9%). Surprisingly, MAP infection was detected at a higher rate in samples with rs2910164 GC (67%) compared to samples with normal genotype (33%).ConclusionsThe data clearly associates miR-146a rs2910164 GC with an overactive immune response and increases the risk to acquire infection. The study is even more relevant now in our efforts to understand susceptibility to SARS-CoV-2 infection and the development of COVID-19. This study suggests that genetic variations among COVID-19 patients may predict who is at a higher risk of acquiring infection, developing exacerbating symptoms, and possibly death. A high scale study with more clinical samples from different disease groups is planned.

Association of miR-196a2 and miR-149 single-nucleotide polymorphisms with atherosclerotic ischemic stroke susceptibility

BackgroundBeside 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.ObjectivesInvestigate 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 methodsOne 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.ResultsThe 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 0.005) and C allele was associated with about 1.9 fold risk of stroke (OR 1.909, P 0.002). Haplotypes analysis revealed miR-196a2T/-149 T allele combination was significantly lower among stroke patients than the controls (P < 0.001) with a protective effect (OR 0.196, 95% CI 0.083-0.466).ConclusionA decrease in the incidence of ischemic stroke is associated with miR-196a2 TT genotype and T allele and increases in the likelihood risk of ischemic stroke are associated with CC genotype and C allele within miR-149, and the two miRNAs under study are closely associated with vascular damage responses.

Association of miR-146a polymorphism rs2910164 and type 2 diabetes risk: a meta-analysis.

ObjectiveCirculating miR-146a is aberrantly expressed in patients with type 2 diabetes (T2D), probably resulting from gene polymorphisms. However, the role of polymorphism rs2910164 in T2D pathogenesis remains controversial. Thus, we designed a meta-analysis to investigate the association between rs2910164 and T2D.MethodsPubMed and Embase were searched for eligible papers in English published through September 2, 2019. Random or fixed effect models were used to determine risk estimates according to heterogeneities.ResultsFour studies, involving 2,069 patients and 1,950 controls, were included. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to pool the effect size. The pooled ORs and 95% CIs were 1.501 (0.887–2.541), 1.102 (0.931–1.304), 1.276 (0.900–1.811), 1.204 (0.878–1.652), 1.238 (0.880–1.740), and 1.350 (0.904–2.016) under the homozygote, heterozygote (CG vs. GG and CC vs. CG), dominant, allele, and recessive models, respectively. Heterogeneity was detected in most genetic models, with subgroup analyses performed by ethnicity, genotyping method, and disease duration. The co-dominant model was determined to be the most appropriate genetic model.ConclusionsOur findings suggested that polymorphism rs2910164 is not correlated with T2D susceptibility. However, the results should be interpreted with caution because of confounding factors.