microRNA Polymorphisms Research Articles

Polymorphism rs2682818 participates in the progression of colorectal carcinoma via miR-618-TIMP1 regulatory axis

Colorectal carcinoma (CRC) has a high morbidity and mortality. Current studies have confirmed a variety of microRNA polymorphisms were associated with tumor susceptibility, however, the mechanisms are still unknown. In this study, we were aimed to clarify how polymorphism rs2682818 participated in the progression of CRC. First of all, the differential expression of miR-618 was assessed by quantitative real-time polymerase chain reaction in CRC patients with different genotypes of polymorphism rs2682818, including homozygous (TT) genotype, homozygous (GG) genotype and heterozygous (TG) genotype. Secondly, plasmids carried miR-168 precursor sequences harboring rs2682818 (SNP type) or without rs2682818 (wild type) were transfected into 293T cells to verify that polymorphism rs2682818 affected miR-618 expression. Thirdly, CCK-8 assay, flow cytometry assay, transwell assay and mouse xenograft assay were performed to measure the biological functions of miR-618 in CRC. Fourthly, the candidate target genes of miR-618 which were predicted by bioinformatics tools were verified by luciferase reporter assay. Finally, in order to explain the potential molecular mechanisms, western blotting was performed to demonstrate the differential expression and phosphorylation of pathway related proteins. The results showed that miR-618 was down-regulated in colon cancer, especially in CRC patients with rs2682818 GG homozygous genotype. Higher expression of mature miR-618 occurred in patients with TT homozygous genotype, and these patients usually had a longer survival time. Moreover, miR-618 mimic obviously impaired the growth and invasion ability of CRC cells, and miR-618 mimic also remarkably promoted CRC cell apoptosis. Our luciferase experiments confirmed that TIMP1 was a target of miR-618 in CRC cells. Knockdown of TIMP1 also significantly inhibited the malignant cytological features of CRC, including malignant growth and invasion as well as apoptosis resistance. In summary, polymorphism rs2682818 participated in the progression of CRC via affecting the expression of mature miR-618 in CRC cells, and miR-618 inhibited the progression of CRC via targeting TIMP1expression.

Relationship of microRNA locus with type 2 diabetes mellitus: a case–control study

Type 2 diabetes mellitus (T2DM) is considered as a metabolic disease with hyperglycemia. Accumulating investigations have explored the important role of hereditary factors for T2DM occurrence. Some functional microRNA (miR) polymorphisms may affect their interactions with target mRNAs and result in an aberrant expression. Thus, miR variants might be considered as a biomarker of the susceptibility of T2DM. In this study, we recruited 502 T2DM cases and 782 healthy subjects. We selected miR-146a rs2910164 C>G, miR-196a2 rs11614913 T>C and miR-499 rs3746444 A>G loci and carried out an investigation to identify whether these miR loci could influence T2DM occurrence. In this investigation, a Bonferroni correction was harnessed. After adjustment, we found that rs2910164 SNP was a protective factor for T2DM (GG vs CC/CG: adjusted P = 0.010), especially in never drinking (GG vs CC/CG: adjusted P = 0.001) and BMI ≥24 kg/m2 (GG vs CC/CG: adjusted P = 0.002) subgroups. We also identified that rs11614913 SNP was a protective factor for T2DM in smoking subjects (CC/TC vs TT: adjusted P = 0.002). When we analyzed an interaction of SNP–SNP with the susceptibility tof T2DM, rs11614913/rs3746444, rs2910164/rs3746444 and rs11614913/rs2910164 combinations were not associated with the risk of T2DM. In summary, this study highlights that rs2910164 SNP decreases the susceptibility of T2DM, especially in BMI ≥24 kg/m2 and never drinking subgroups. In addition, we also identify that rs11614913 C allele decreases the susceptibility of T2DM significantly in smoking subgroup.

Genetics, Epigenetics, and Gender Impact in Axial-Spondyloarthritis Susceptibility: An Update on Genetic Polymorphisms and Their Sex Related Associations.

Spondyloarthritis (SpA) is a group of chronic inflammatory rheumatic disease that can be divided into predominantly axial or predominantly peripheral involvement, with or without associated psoriasis, inflammatory bowel disease or previous infection. Axial SpA (axSpA) encompasses ankylosing spondylitis (AS) with radiological sacroiliitis, and a type without radiographic sacroiliitis, called “non-radiographic axial SpA” (nr-axSpA). Males and females show large differences in their susceptibility to SpA, such as distinctions in clinical patterns, phenotypes and in therapeutical response, particularly to TNF inhibitors (TNFi). Several studies indicate that AS women have doubled risk to failure TNFi compared with males. This diversity in drugs’ efficacy among women and men may be caused by differences in the balance of sex hormones and in gene-specific expression likely triggered by X-chromosome instability and gene-specific epigenetic modifications. Evidence reported that polymorphisms in microRNAs on X- and other chromosomes, such as miR-146a, miR-155, miR-125a-5p, miR-151a-3p and miR-22-3p, miR-199a-5p could be involved in the different clinical presentation of SpA, as well as disease activity. In addition, association with non−response to TNFi treatment and presence of IRAK3 and CHUCK genes in SpA patients was recently detected. Finally, polymorphisms in genes involved in IL-23/IL-17 pathway, such as in drug pharmacodynamics and pharmacokinetics may have a role in response to TNFi, IL17i, and IL23i. A major understanding of genomic variability could help in the development of new therapeutic targets or in taking advantages of different mechanisms of action of biological drugs. Moving from the multifactorial etiology of disease, the present review aims at evaluating genetic and epigenetic factors and their relationship with sex and bDMARDs response, helping to investigate the different expression among males and females of genes on X- and other chromosomes, as well as mi-RNA, to highlight relationships between sex and occurrence of specific phenotypes and symptoms of the disease. Moreover, the role of the epigenetic modification in relation to immune-regulatory mechanisms will be evaluated.

3'-UTR Polymorphisms in Thymidylate Synthase with Colorectal Cancer Prevalence and Prognosis.

Colorectal cancer (CRC) is the third most common type of cancer and the second leading cause of cancer-related mortality in Western countries. Polymorphisms in one-carbon metabolism and angiogenesis-related genes have been shown to play important roles in tumor development, progression, and metastasis for many cancers, including CRC. Moreover, recent studies have reported that polymorphisms in specific microRNA (miRNA)-binding regions, which are located in the 3′-untranslated region (UTR) of miRNA-regulated genes, are present in a variety of cancers. Here, we investigated the association between two thymidylate synthase (TYMS or TS) 3′-UTR polymorphisms, 1100T>C [rs699517] and 1170A>G [rs2790], and CRC susceptibility and progression in Korean patients. A total of 450 CRC patients and 400 healthy controls were enrolled in this study, and genotyping at the TS locus was performed by polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) or TaqMan allelic discrimination assays. We found that TS 1170A>G genotypes, as well as the TS 1100T-1170G and 1100C-1170A haplotypes, are strongly associated with CRC. The TS 1100TC+CC type was associated with a poor survival (OS and RFS) rate. In addition, levels of the TS 1100C and TS 1170G allele were found to be significantly increased in CRC tissue. Our study provides the first evidence for 3′-UTR variants in TS genes as potential biomarkers of CRC prognosis and prevention.

Meta-analysis of association of microRNAs genetic variants with susceptibility to rheumatoid arthritis and systemic lupus erythematosus.

Background:An increasing body of studies has investigated that genetic polymorphisms in microRNA (miRNA) may be related to susceptibility to rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). However, some results remain controversial. Thus, a meta-analysis was embarked on assessing whether some miRNA polymorphisms are associated with the risk of RA and SLE.Methods:Relevant studies were acquired on PubMed, Web of Science, Cochrane Library, CNKI, and Embase electronic databases from inception to December 2019. The strength of the association of miRNA polymorphisms with the risk of RA and SLE was assessed by odds ratios (ORs) and 95% confidence intervals (CIs).Results:Eligible 20 articles (36 studies) involving 5 miRNAs were enrolled in the meta-analysis. For RA, the polled result showed that there was no significant relationship between miR-146a rs2910164 and RA, but subgroup analysis based on ethnicity demonstrated that CC genotype may be a genetic protect factor for RA in Caucasians (CC vs CG+GG, OR = 0.825, 95% CI: 0.684–0.996, Pz = .045, Ph = .166). Besides, statistical significance of miR-499 rs3746444 (T/C) with susceptibility to RA was observed as well in the overall population, and the association was only significant in Caucasians but not Asians. For SLE, the associations of miR-146a rs2431697 T allele/T-carrier with increased risk of SLE were observed.Conclusions:Our results highlight that miR-499 rs3746444 may contribute to RA susceptibility, particularly in Caucasians. In addition, CC genotype in miR-146a rs2910164 may act as a protector of RA in Caucasians. For SLE, miR-146a rs2431697 (C/T) is most likely to the increased the risk of SLE. These findings do not support the genetic association between miR-196a2 rs11614913 and RA/SLE susceptibility, as well as the association of miR-146a rs2910164, miR-146a rs57095329, miR-499 rs3746444 with SLE.

The relationship between polymorphisms of microRNA and preeclampsia: A protocol for meta-analysis and bioinformatics prediction.

Background:Preeclampsia has genetic correlation. Many studies have shown that microRNA (miRNA) polymorphism is highly associated with preeclampsia, but the results are inconsistent. The purpose of this study is to systematically evaluate the relationship between miRNA polymorphism and preeclampsia.Methods:In this study, the search time is set from the establishment of the database on January 2021. The search database include China National Knowledge Infrastructure (CNKI), Wanfang, VIP and China Biology Medicine disc (CBM), PubMed, EMBASE, and Web of Science, and the Cochrane Library. The subjects are case-control studies on the relationship between miRNA polymorphism and preeclampsia. The language is limited to English and Chinese. The data of the included study are extracted and the literature quality is evaluated by 2 researchers independently. The data are statistically analyzed through Stata 16.0 software. We also predicted the miRNA secondary structure and the binding sites of miRNA interaction with its target genesResults:This review will be disseminated in print by peer-review.Conclusion:This study will provide evidence-based medicine to elucidate the genetic tendency of preeclampsia.Ethics and dissemination:Private information from individuals will not be published. This systematic review also does not involve endangering participant rights. Ethical approval will not be required. The results may be published in a peer-reviewed journal or disseminated at relevant conferences.OSF Registration number:DOI 10.17605/OSF.IO/MJY2X.

Functional miR29a polymorphism is associated with protection against recurrent spontaneous abortion: A case-control study and bioinformatics analysis

Recurrent spontaneous abortion (RSA) is a multifactorial disorder, and multiple genetic and environmental factors affect its pathogenesis. Recently, microRNA polymorphisms have been significantly associated with RSA incidence. This study aimed to evaluate the impact of miR29a rs157907A/G variant on RSA risk. A total of 338 subjects were enrolled in the study. Genotyping was carried out by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Bioinformatics databases were used for the analysis of the gene-miRNA interaction network. We found that miR29a rs157907A/G polymorphism was associated with strong protection against RSA, under codominant AG (OR = 0.13), dominant AG + GG vs. AA (OR = 0.20), overdominant AG vs. AA+GG (OR = 0.14), and allelic (OR = 0.31) contrasted models. Besides, the association between this variant and RSA did not differ between various ages (<35 and ≥35) and Body Mass Index (<30 and ≥30). In-silico analysis revealed that miR-29a targets several genes involved in cell cycles, angiogenic signaling, and apoptosis of trophoblastic cells. Our findings suggest that miR29a rs157907A/G polymorphism might reduce the risk of RSA in an Iranian population. Replication studies are needed to reveal the precise role of miR29a in the development of placental disorders.

MALAT1 rs619586 A/G polymorphisms are associated with decreased risk of lung cancer.

Lung cancer is the leading cause of cancer-associated mortality worldwide. Genetic factors are reported to play important roles in lung carcinogenesis. To evaluate genetic susceptibility, we conducted a hospital-based case-control study on the effects of functional single nucleotide polymorphisms (SNPs) in long non-coding RNAs (lncRNAs) and microRNAs on lung cancer development. A total of 917 lung cancer cases and 925 control subjects were recruited. The MALAT1 rs619586 A/G genotype frequencies between patient and control groups were significantly different (P < .001), specifically, 83.85% vs 75.88% (AA), 15.60% vs 21.79% (AG), and 0.55% vs 2.32% (GG). When the homozygous genotype MALAT1 rs619586 AA was used as the reference group, AG (AG vs AA: adjusted odds ratio [OR] 0.65, 95% confidential interval [CI] 0.51–0.83, P = .001) and GG genotypes were associated with significantly decreased risk of lung cancer (GG vs AA: adjusted OR 0.22, 95% CI 0.08–0.59, P = .003). In the dominant model, MALAT1 rs619586 AG/GG variants were also associated with a significantly decreased risk of lung cancer (adjusted OR 0.61, 95% CI 0.48–0.78, P < .001). In the recessive model, when MALAT1 rs619586 AA/AG genotypes were used as the reference group, the GG homozygous genotype was also associated with significantly decreased risk for lung cancer (adjusted OR 0.24, 95% CI 0.09–0.64, P = .004). Hsa-miR-34b/c rs4938723 T > C, pri-miR-124-1 rs531564 C > G and hsa-miR-423 rs6505162 C > A SNPs were not associated with lung cancer risk. Our collective data indicated that MALAT1 rs619586 A/G SNPs significantly reduced the risk of lung cancer. Large-scale studies on different ethnic populations and tissue-specific biological characterization are required to validate the current findings.

MicroRNA polymorphism: A target for diagnosis and prognosis of hepatocellular carcinoma?

Hepatocellular carcinoma (HCC) is a life-threatening cancer of the digestive system, with complex pathogenesis affected by a broad spectrum of genetic and epigenetic factors. Among several factors, microRNAs (miRNAs), which are considered regulators of the post-transcriptional gene expression, play important roles in determining the malignant phenotype of HCC. In recent years, the advances in molecular genetics have resulted in the characterization of complex genetic factors and in the identification of epigenetic mechanisms of diseases. Accumulating data have suggested that miRNA polymorphisms are involved in tumorigenesis and prognosis, suggesting that the miRNAs may serve as a target for HCC with regard to pathogenesis and prognosis. In the present review, a comprehensive and detailed literature search was conducted and the role of miRNA polymorphisms in the pathogenesis and prognosis of HCC is summarized. The data proposed the use of miRNAs as targets for the diagnosis and treatment of HCC.

ДИАГНОСТИЧЕСКОЕ ЗНАЧЕНИЕ ЛАБОРАТОРНЫХ МАРКЕРОВ НЕОНАТАЛЬНОГО СЕПСИСА У НЕДОНОШЕННЫХ ДЕТЕЙ

Neonatal sepsis (NS) is the leading cause of mortality in premature newborns. It is a difficult diagnostic task for clinicians. This article provides a review of the literature on laboratory markers of NS. The latest methods for the diagnosis of sepsis in premature infants in various studies are considered in the article. The results of studying the diagnostic value of a general blood test, cytokines, C-reactive protein, procalcitonin, prespepsin, microRNA polymorphism, bacterial blood culture, their advantages and disadvantages, as well as diagnostic significance – sensitivity, specificity, prognostic value of positive and negative results are presented.

Association of Genetic Polymorphisms in MicroRNAs With Type 2 Diabetes Mellitus in a Chinese Population.

IntroductionMicroRNAs (miRNA) involved in the insulin signaling pathways deeply affect the pathogenesis of T2DM. The aim of this study was to assess the association between single nucleotide polymorphisms (SNP) of the related miRNAs (let-7f rs10877887, let-7a-1 rs13293512, miR-133a-1 rs8089787, miR-133a-2 rs13040413, and miR-27a rs895819) and susceptibility to type 2 diabetes mellitus (T2DM), and its possible mechanisms.MethodsFive SNPs in miRNAs (let-7f rs10877887, let-7a-1 rs13293512, miR-133a-1 rs8089787, miR-133a-2 rs13040413, and miR-27a rs895819) involved in the insulin signaling pathways were selected and genotyped in a case-control study that enrolled 371 T2DM patients and 381 non-diabetic controls. The individual SNP association analyses, interaction analyses of SNP-SNP, SNP-environmental factors were performed. The effect the risk-associated polymorphism on regulating its mature miRNA expression was also evaluated.ResultsIn overall analyses, miR-133a-2 rs13040413 and let-7a-1 rs13293512 were related to the susceptibility to T2DM. In stratified analyses, miR-133a-2 rs13040413, let-7a-1 rs13293512 and miR-27a rs895819 showed associations with T2DM in the age ≥ 60 years subgroup. Moreover, let-7a-1 rs13293512 and miR-27a rs895819 showed associations with T2DM in male subgroup. In SNP-environmental factors interaction analyses, there were interaction effects of miR-133a-2 rs13040413 with dyslipidemia, let-7a-1 rs13293512 with smoking, and let-7a-1 rs13293512 with dyslipidemia on T2DM. In SNP-SNP interaction analyses, there were also interaction effects of miR-133a-1 rs8089787 with let-7a-1 rs13293512, and miR-133a-1 rs8089787 with let-7f rs10877887 on T2DM. Furthermore, for miR-133a-2 rs13040413, the variant T allele showed a trend toward decreased miR-133a expression in comparison with the wild C allele. For let-7a-1 rs13293512, the variant C allele expressed a lower let-7a compared to the wild T allele.ConclusionMiRNAs polymorphisms involved in the insulin signaling pathways and the interaction effects of SNP-SNP, SNP-environmental factors were related to T2DM susceptibility in a Chinese population.

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 association between polymorphisms in miRNA and the cholinesterase activity of workers in an omethoate-exposed environment

ABSTRACT To explore the association between polymorphisms in microRNAs (miRNAs) and the cholinesterase (ChE) activity in omethoate-exposed workers, we recruited 180 omethoate-exposed workers and 115 controls to measure their ChE activity using acetylcholine and dithio-bis-(nitrobenzoic acid) and genotype susceptible SNPs in their miRNA by time-of-flight mass spectrometry. ChE activity in the exposure group was lower than that in the control group (P < 0.001). The analysis of covariance result showed that ChE activity was lower in the (- -/- T) genotype in miR-30a rs111456995 (1.97 ± 0.47) than in the TT genotype (2.23 ± 0.59) of the exposure group (P = 0.004). Multivariate linear regression was performed to find influencing factors on ChE activity, and variables kept in the model included omethoate exposure (b = −1.094, P < 0.001), gender (b = −0.381, P < 0.001), miR-30a rs111456995 (- -/- T)(b = −0.248, P < 0.001), and drinking (b = 0.258, P =0.019). The results suggest that individuals carrying a (- -/- T) genotype in miR-30a rs111456995 were more susceptible to damage in their cholinesterase induced by omethoate exposure.

A case-control study of microRNA polymorphisms in gastric cancer screening by SNP chip combined with time of flight mass spectrometry.

Aims: To explore newSNPsites of miRNAsassociated with gastric cancer, thereby providing valuable biomarkers to diagnose and screen gastric cancer. Materials & methods: A 1:1 case-control study was carried out. Microarrays were used to screen the SNP loci of miRNAs in the genomes of matched pairs of patients, 96 with gastric cancer and 96 healthy controls. For validation, mass spectrometry was used to classify miRNA SNP loci in 622 pairs of subjects. Results: rs7143252 was linked to a higher occurrence of gastric cancer. Conclusion: These results suggest that rs7143252 could be used as a specific biomarker to diagnose and screen gastric cancer.

A Genome-Wide Study of Single-Nucleotide Polymorphisms in MicroRNAs and Further In Silico Analysis Reveals Their Putative Role in Susceptibility to Late-Onset Alzheimer's Disease.

Late-onset Alzheimer's disease (LOAD) is a neurodegenerative disorder of growing relevance in an aging society for which predictive biomarkers are needed. Many genes involved in LOAD are tightly controlled by microRNAs (miRNAs), which can be modulated by single-nucleotide polymorphisms (SNPs). Our aim was to determine the association between SNPs in miRNAs and LOAD. We selected all SNPs in pre-miRNAs with a minor allele frequency (MAF) > 1% and genotyped them in a cohort of 229 individuals diagnosed with LOAD and 237 unrelated healthy controls. In silico analyses were performed to predict the effect of SNPs on miRNA stability and detect downstream pathways. Four SNPs were associated with LOAD risk with a p value < 0.01 (rs74704964 in hsa-miR-518d, rs71363366 in hsa-miR-1283-2, rs11983381 in hsa-miR-4653, and rs10934682 in hsa-miR-544b). In silico analyses support a possible functional effect of those SNPs in miRNA levels and in the regulation of pathways of relevance for the development of LOAD. Although the results are promising, additional studies are needed to validate the association between SNPs in miRNAs and the risk of developing LOAD. Graphical abstract.

Significant Association between Microrna Gene Polymorphisms and Type 2 Diabetes Mellitus Susceptibility in Asian Population: A Meta-Analysis

The gene polymorphisms in microRNA might relate to susceptibility of type 2 diabetes mellitus (T2DM). However, the results of existing studies were inconsistent and obscure. To investigate the precise associations between microRNA gene polymorphisms and T2DM risk, the present meta-analysis was performed. The literatures were searched from four electronic databases, PubMed, Embase, CNKI and Wan-fang. Subsequently, odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were both used to evaluate the associations between two single nucleotide polymorphisms (SNPs) (microRNA146a rs2910164 (G>C), microRNA124a rs531564 (C>G)) and risk of T2DM in Asian population. Totally, there were 4 studies included in our present analysis in the language of English and Chinese. There were partly significant associations between susceptibility of T2DM and SNPs (microRNA146a rs2910164 (G>C), microRNA124a rs531564 (C>G)). The G allele in microRNA146a rs2910164 (G>C) and C allele in microRNA124a rs531564 (C>G) both presented remarkably reduced risk of T2DM when compared with the healthy population. The microRNA146a rs2910164 (G allele) and microRNA124a rs531564 (C allele) might function as protective factors in the pathogenetic process of T2DM in Asian population.

Study of the Association Between microRNA (miR-25T>C, miR-32C>A, miR-125C>T, and miR-222G>T) Polymorphisms and the Risk of Recurrent Pregnancy Loss in Korean Women.

Recurrent pregnancy loss (RPL), which is defined as two pregnancy losses that occur before 20 weeks of gestation, is relatively common, occurring in approximately 1–5% of women. The underlying cause is often unclear, although numerous factors may contribute to RPL, including environmental and immunological factors, blood coagulation disorders, and genetics. In particular, single nucleotide variants have been associated with RPL, including those found in microRNAs (miRNAs). We investigated the association between four miRNA polymorphisms, miR-25T>C, miR-32C>A, miR-125aC>T, and miR-222G>T, and RPL in a cohort consisting of 361 RPL patients and 272 controls. Subjects were genotyped at miRNA loci by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis, and genotype frequencies were calculated. We then performed allele and genotype combination analyses and measured the association between miRNA polymorphisms and clinical variables in both RPL patients and controls. We detected a statistically significant association between RPL and the miR-25T/miR-32C/miR-125aT/miR-222T allele combination (adjusted odds ratio (AOR), 4.361; 95% confidence interval (CI), 1.496–12.72; P = 0.003). Three-gene combinations, including miR-32C/miR-125aT/miR-222T (AOR, 3.085; 95% CI, 1.254–7.588; P = 0.010) and miR-25T/miR-125aT/miR-222T (AOR, 2.929; 95% CI, 1.183–7.257; P = 0.015), and the two-gene combination miR-125aT/miR-222T (AOR, 2.417; 95% CI, 1.084–5.386; P = 0.026) were also associated with RPL. Analysis of variance (ANOVA) revealed that platelet counts and blood urea nitrogen levels were significantly different in RPL patients expressing different miR-125aC>T and miR-25T>C genotypes, respectively (P < 0.05). In addition, creatinine levels were lower in RPL patients expressing the minor alleles miR-25T>C and miR-32C>A. We investigated miRNAs (miR-25, miR-32, miR-125a, miR-222) in RPL patients and healthy controls. Significantly different allele frequencies were detected by ANOVA. We suggest that miRNAs and clinical factors can impact RPL occurrence.

MiRNA polymorphisms and risk of premature coronary artery disease

ObjectiveSeveral microRNA (miRNA) polymorphisms have been associated with susceptibility to specific health disorders, including cardiovascular diseases. The aim of the present study was to investigate whether four well-studied miRNA polymorphisms in non-Caucasian populations, namely miR146a G>C (rs2910164), miR149 C>T (rs2292832), miR196a2 C>T (rs11614913) and miR499 A>G (rs3746444), contribute to the risk for the development of premature Coronary Artery Disease (CAD) in the Greek population. MethodsWe used a case-control study to examine these associations in 400 individuals: 200 CAD patients [including a subgroup of myocardial infraction (MI) patients] and 200 healthy controls, all of Greek origin. MiRNA polymorphisms were genotyped using three different assays: Polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP), High resolution Melting (HRM) and Sanger sequencing. ResultsTwo of these polymorphisms, miR196a2 C>T (rs11614913) and miR499 A>G (rs3746444) were found to be strongly associated with increased risk for CAD (p=0.0388 and p=0.0013, respectively) and for MI (p=0.0281 and p=0.0273, respectively). Furthermore, miR146C-miR149C-miR196T-miR499G allele combination appeared to be significantly related to CAD (p=0.0185) and MI (p=0.0337) prevalence. ConclusionsOur results suggest that at least two of the studied polymorphisms, miR196a2 C>T (rs11614913) and miR499 A>G (rs3746444), as well as the miR146C-miR149C-miR196T-miR499G allele combination could represent useful biomarkers of CAD and/or MI susceptibility in the Greek population. These special genetic characteristics, in combination with environmental factors and personal habits, might contribute to CAD and/or MI prevalence.

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...

Epidemiological evidence for associations between variants in microRNA or biosynthesis genes and lung cancer risk.

In the past decade, the studies involving single nucleotide polymorphisms (SNPs) in microRNAs (miRNAs) with lung cancer (LC) risk have been performed, however, these results are inconsistent, and a systematic research synopsis has not been performed yet. Therefore, we attempted to perform comprehensive meta‐analyses to assess the relationships between SNPs in miRNAs or biosynthesis genes and LC risk and further evaluate the epidemiological credibility of these significant associations. We used PubMed, Medline, and Web of Science to search for relevant articles published before 30 May 2019 that assessed relationships between SNPs in miRNAs or biosynthesis genes and LC risk. The cumulative epidemiological evidence of statistical relationships was further assessed combining Venice Criteria and a false‐positive report probability test. Based on 20 publications with 15 969 cases and 17 174 controls, we found that six variants in miRNAs or biosynthesis genes that proved significant associations with LC risk, whereas five proved no association. Subgroup analyses by ethnicity and genetic models were performed, suggesting that four associations were rated as demonstrating strong evidence of relationship with LC risk, including miRNA‐146a rs2910164 in all populations under dominant model and in Asians under dominant and recessive models, and AGO1 rs595961 in Asians under allelic model. Three associations were graded as moderate, and seven associations were rated as weak. This study presents the relationships between SNPs in miRNAs or biosynthesis genes and LC risk, subsequently demonstrates the credibility of these significant associations, and highlights the role in the pathogenesis of LC.