miRNA Single Nucleotide Polymorphisms Research Articles

MiRNA polymorphisms affect the prognosis of gastric cancer: insights from Xianyou, Fujian

IntroductionGastric cancer, characterized by high incidence and substantial disease burden, has drawn continuous attention regarding its occurrence and prognosis. Genetics plays a crucial role in influencing the prognosis of gastric cancer, and single nucleotide polymorphisms are closely associated with the occurrence, development, and prognosis of this malignant tumor. Our study aims to conduct survival analysis on patients carrying different single nucleotide polymorphisms, exploring the relationship between miRNA single nucleotide polymorphisms and the prognosis of gastric cancer.MethodsGenetic data from 344 patients in Xianyou, Fujian, formed the basis of our study. We delineated the survival rate and median survival time, utilizing the log-rank test and COX regression analysis as statistical tools.ResultsUpon stratifying the data by sex or operation, it was discerned that the GG genotype at MSH2 rs17502941 independently posed a heightened risk for gastric cancer. Other stratification analyses suggested that the subsequent single nucleotide polymorphisms were correlated with patient prognosis: rs17502941, rs884225, rs1468063, rs7143252, and rs2271738.DiscussionThe outcomes of this study strongly suggest that miRNA polymorphisms significantly influence the survival time of gastric cancer patients and can serve as effective predictors for the prognosis of gastric cancer.

MiR-499a rs3746444 A>G Polymorphism Is Correlated with Type 2 Diabetes Mellitus and Diabetic Polyneuropathy in a Romanian Cohort: A Preliminary Study.

Type 2 diabetes mellitus (T2DM) is a common metabolic disorder that results from complex interactions of both environmental and genetic factors. Many single nucleotide polymorphisms (SNPs), including noncoding RNA genes, have been investigated for their association with susceptibility to T2DM and its complications, with little evidence available regarding Caucasians. The aim of the present study was to establish whether four miRNA SNPs (miR-27a rs895819 T>C, miR-146a rs2910164 G>C, miR-196a2 rs11614913 C>T, and miR-499a rs3746444 A>G) are correlated with susceptibility to T2DM and/or diabetic polyneuropathy (DPN) in a Romanian population. A total of 167 adult T2DM patients and 324 age- and sex-matched healthy controls were included in our study. miRNA SNPs were detected by real-time PCR using a TaqMan genotyping assay. A significant association with T2DM was observed only for the miR-499a rs3746444 A>G SNP in all the tested models, and the frequencies of both the miR-499a rs3746444 AG and the GG genotypes were higher in the T2DM patients compared to the controls. No correlation was observed for the miR-27a rs895819 T>C, miR-146a rs2910164 G>C, or miR-196a2 rs11614913 C>T SNPs in any genetic model. When we assessed the association of these SNPs with DPN separately, we found a positive association for the miR-499a rs3746444 SNP in both codominant and dominant models (OR 6.47, 95% CI: 1.71-24.47; OR 2.30, 95% CI: 1.23-4.29, respectively). In conclusion, this study shows that miR-499a rs3746444 A>G may influence both T2DM and DPN susceptibility, with carriers of the GG genotype and the G allele being at an increased risk in the Romanian population.

The SNP rs4591246 in pri-miR-1-3p is associated with abdominal aortic aneurysm risk by regulating cell phenotypic transformation via the miR-1-3p/TLR4 axis

Emerging evidence reveals that single nucleotide polymorphism (SNP) within miRNAs can affect the risk of cardiovascular diseases. However, the role of miRNA SNPs in abdominal aortic aneurysm (AAA) is unclear. This study aimed to determine the association between SNPs in pri-miR-1-3p and AAA risk, as well as its underlying molecular mechanism. SNP genotyping was performed in 335 AAA patients and 335 controls using the KASP method and tissue miR-1-3p expression was measured by qRT-PCR. The biological effects of significant SNP were validated using in vitro studies. We found that the rs4591246 variant genotype was correlated with increased AAA risk and tissue miR-1-3p expression was reduced in AAA patients as compared with control subjects. An in silico approach predicted that the rs4591246 polymorphism altered the secondary structure and stability of pri-miR-1-3p, and in vitro evidence suggested that the rs4591246 polymorphism affected mature miR-1-3p expression. And luciferase assays verified TLR4 as a direct target gene of miR-1-3p. Further functional experiments demonstrated that the rs4591246 variant genotype could promote Ang II-induced cell phenotypic switching by suppressing mature miR-1-3p expression and in turn upregulating TLR4 expression, but this effect was rescued in the presence of TLR4 siRNA. In conclusion, as a promising genetic biomarker for AAA susceptibility, the SNP rs4591246 may exert its effects on AAA risk by regulating cell phenotypic transformation via the miR-1-3p/TLR4 axis.

MicroRNA sequence variation can impact interactions with target mRNA in cattle

BackgroundSmall non-coding microRNAs (miRNAs) are important modulators at post-transcriptional levels. Single-nucleotide polymorphisms (SNPs) located in miRNA genes can alter the secondary structure of pre-miRNA to either impair or promote the miRNA maturation processes. Furthermore, SNPs located in the miRNA seed regions can stabilize or disturb miRNA-target interactions, thereby, quantitatively influence the expression of target genes. Therefore, the main objective of this study was to detect SNPs in bovine miRNAs using the whole-genome re-sequencing datasets of 1632 cattle of five breeds from the 1000 bull genomes project. ResultsIn total, our study identified 1109, 334, and 130 SNPs in the miRNA precursor, mature, and seed regions, respectively. The heterozygosity values were generally less than 0.3, and the minor allele frequencies (MAFs) were mainly less than 0.1. Most SNPs were in Hardy-Weinberg equilibrium (HWE) (HWE-P > 0.05). Furthermore, we found that the majority of SNPs (MAF > 0.1 and HWE-P > 0.05) in the miRNA seed regions altered the repertoire of target genes, which in turn were enriched in different KEGG pathways or GO terms. Thus target prediction for bta-miR-2888 revealed loss of 309 target genes and gain of 691 target genes. The 691 gained target genes were significantly enriched in 60 KEGG pathways and 21 GO terms. ConclusionIn summary, our study identified candidate SNPs in miRNA precursor, mature, and seed regions that are likely to affect target RNA interactions, thereby potentially influencing cattle phenotypic traits.

Association of microRNA gene polymorphisms with recurrent spontaneous abortion: An updated meta‑analysis.

Numerous studies have reported single nucleotide polymorphisms (SNPs) in microRNAs (miRNAs) associated with unexplained recurrent spontaneous abortion (URSA). The present study aimed to conduct an updated meta-analysis to confirm a pooled effect size of the association between miRNA SNPs and URSA. The relevant literature was searched on PubMed, EMBASE, Web of Science and Cochrane Library before July 2022 to identify case-control studies. The pooled odds ratio and confidence intervals at 95% of the eligible studies were extracted and evaluated under five genetic models. A total of 18 studies involving 3,850 cases and 4,312 controls were included. miR499a rs3746444 A>G, miR-149 rs2292832 T>C, miR-125a rs41275794 G>A and miR-10a rs3809783 A>T may enhance the risk of recurrent spontaneous abortion (RSA) under various genetic models. Although no separate association was found between the miR-125a rs12976445 C>T and miR-27a rs895819 A>G polymorphisms and RSA, statistical significance was found in certain ethnic groups only. The current analysis suggests a high significance of an up-to-date meta-analysis for screening out and preventing URSA among high-risk women by testing miRNA SNPs and RSA susceptibility.

Investigation of the effects of mir-219-1 gene variants on the development of disease in non-small cell lung cancer patients.

Various variants of the miR-219-1 gene are one of the first genes associated with NSCLC prognosis in the literature. We aimed to genotype two different variants of the miR-219-1 gene and to investigate to using of the result as a biomarker in the diagnosis and treatment of NSCLC. The patients were chosen according to International NSCLC criteria and genomic DNA was isolated from blood (138 patients and 100 healthy individuals). Then qRT-PCR was applied to determine the rs213210 and rs421446 variants of miR-219-1 gene polymorphisms. Allele and genotype frequencies were compared using Pearson's chi-square and Fisher's exact tests test. We found that TT genotype (p=0,381) in rs213210 compared with CC genotype (p=0,165) and CC genotype (p=0,823) in rs421446 compared with TT genotype (p=0,537) did not show a significantly increased risk of NSCLC. There is no relationship between polymorphisms in miR-219-1 and the outcome of NSCLC. miRNA single nucleotide polymorphisms can be used as genetic biomarkers to predict cancer susceptibility, early diagnosis, and prognosis. Our study has shown that two variants of miR-219-1 were not related to NSCLC in the Turkish population. The reason for this can be differences in ethnicity, regions, and background of population and these differences could lead to various outcomes.

Association Between Single Nucleotide Polymorphisms of miRNAs and Gastric Cancer: A Scoping Review.

Background: Gastric cancer (GC) is the third leading cause of cancer-related mortality worldwide, and single nucleotide polymorphisms (SNPs) in microRNAs (miRNAs) are believed to affect the occurrence and progression of cancer by altering the expression and biological functions of miRNAs. Methods: The present scoping review was designed to evaluate and discuss microRNA SNPs (miR-SNPs) that have been found to be associated with GC in the following two contexts: (1) the biological effects on GC based on SNP localization; and (2) the associations between miRNA-SNPs and clinical factors (susceptibility, tumor size, metastasis, overall survival, and prognosis) of GC. Results and Conclusions: Information on miRNAs was collected, including the SNPs, their proven target genes, and the possible impact of the SNPs on GC outcome. Our findings suggest an etiological or modifying role for multiple miRNA SNPs (miR-499, miR-146a, miR-149, miR-148, miR-27a, miR-608, miR-196a-2) in GC and its progression. The findings of this study reinforce the multiple roles of miRNA SNPs in GC.

Relation of genetic polymorphisms in microRNAs with diastolic and systolic function in type 2 diabetes mellitus

Background and aimsType 2 diabetes mellitus (T2DM) has high risk of developing cardiac dysfunction, increasing of either cardiovascular death or hospitalization for heart failure. MicroRNAs (miRNA) affect cardiac function of T2DM. The aim of this study was to investigate the relationships between five miRNA single nucleotide polymorphisms (SNP) and diastolic and systolic function of T2DM. Methods and resultsThree hundred untreated T2DM subjects were included. Each subject underwent SNP genotyping, conventional echocardiography, tissue doppler imaging, and speckle tracking imaging. The effects of miRNA SNPs on diastolic and systolic function were evaluated. The diastolic function of T2DM subjects with miR-133a-1-rs8089787 wild genotype or let-7f-rs10877887 variant genotype was lower than those with miR-133a-1-rs8089787 variant genotype or let-7f-rs10877887 wild genotype, manifesting as higher left atrial volume index, lower mean E′, and higher E/E’ (P < 0.05). There were no significant effects of miR-133a-2-rs13040413, let-7a-1-rs13293512 and miR-27a-rs895819 on the diastolic function of T2DM subjects (P > 0.05). These five miRNA SNPs had no effect on the systolic function of T2DM subjects (P > 0.05). ConclusionsMiRNA-133a-1-rs8089787 and let-7f-rs10877887 were associated with impaired cardiac diastolic function in T2DM. The findings may be a promising therapeutic targets for preventing diastolic dysfunction in T2DM.

MiR-146a, miR-196a2, miR-499, and miR-149 linked with susceptibility to acute lymphoblastic leukemia: A case-control study in Tunisia

BackgroundMicroRNAs (miRNAs) are promising biomarkers of hematological malignancies, including acute lymphoblastic leukaemia (ALL). Recent studies revealed that miRNA single nucleotide polymorphisms (miR-SNP) modulate cancer risk by regulating various signaling pathways. However, their association with altered risk of ALL yielded inconsistent results. ObjectiveThis study aims to investigate the association of four miR-SNPs with altered risk of ALL risk in Tunisian, the first on North African population. MethodsA retrospective case-control study exploring the association of miR-146a, miR-196a2, miR-499, and miR-149 SNPs in 126 ALL patients and 126 healthy controls. ResultsOf the tested variants, significantly lower minor allele frequencies (MAF) of miR-146a C-allele and higher MAF frequency of miR-149 T-allele (P = 0.006) were seen in ALL cases. The association of miR-149 rs2292832 (Pc = 0.02), but not miR-146a rs2910164 (Pc = 0.11) persisted after correcting for multiple comparisons. Significantly reduced prevalence of miR-146a G/C genotype and higher frequency of miR-149 C/T genotype were seen in ALL cases vs. control subjects, which translated into negative association of miR-146a (rs2910164) with ALL according to the codominant and dominant models. Similarly, miR-149 (rs2292832) was positively associated with ALL according to the codominant and dominant genetic models. Three combinations comprising miR-146a/miR-196a2 GG vs CT + TT genotype combination, miR-146a/miR-499 GG vs TC + CC genotype combination, and miR-146a/miR-149 GG vs CT + TT genotype combination, were less frequent in ALL patients than in controls, and were negatively associated with the presence of ALL. ConclusionOur study suggests that miR-146a and miR-149 polymorphisms constitute biomarkers for personalized diagnosis of ALL.

Association between miR-146a rs2910164, miR-196a2 rs11614913, and miR-499 rs3746444 polymorphisms and the risk of esophageal carcinoma: A case-control study.

MicroRNAs (miRNAs) are a group of small, non-coding, and endogenous RNAs that regulate gene expression and over 50% of them are located at cancer-related genomic regions or fragile sites. According to previous studies there is significant association of miRNA single nucleotide polymorphisms (SNPs) with tumorigenesis (e.g., esophageal cancer, hepatocellular cancer, gastric cancer, bladder cancer, breast cancer, lung cancer, and colon cancer), however, the conclusions have been inconsistent. To investigate the relationship between miR-146a rs2910164 C > G, miR-196a2 rs11614913 T > C, and miR-499 rs3746444 A > G polymorphisms and the susceptibility to esophageal squamous cell cancer (ESCC) in the Chinese Han nationality, we recruited 829 cases and 1522 controls in our study. In this case-control study, our results suggest that the rs3746444 GG genotype increased ESCC risk [homozygote model: adjusted odds ratio (OR), 2.26; 95% CI, 1.33-3.83; p=0.003, recessive model: adjusted OR, 2.34; 95% CI, 1.38-3.96; p=0.002], which remained consistent after Bonferroni correction. There was no association of rs11614913 and rs2910164 polymorphisms with ESCC. After adjusting by age, sex, smoking, and drinking status and body mass index (BMI), the multiple logistic analysis suggested that rs11614913 T → C variation reduced ESCC susceptibility in females and in the ≥63 years old subgroups, while rs2910164 C → G variation increased ESCC risk in both two BMI subgroups.

Variability in porcine microRNA genes and its association with mRNA expression and lipid phenotypes

BackgroundMature microRNAs (miRNAs) play an important role in repressing the expression of a wide range of mRNAs. The presence of polymorphic sites in miRNA genes and their corresponding 3′UTR binding sites can disrupt canonical conserved miRNA–mRNA pairings, and thus modify gene expression patterns. However, to date such polymorphic sites in miRNA genes and their association with gene expression phenotypes and complex traits are poorly characterized in pigs.ResultsBy analyzing whole-genome sequences from 120 pigs and wild boars from Europe and Asia, we identified 285 single nucleotide polymorphisms (SNPs) that map to miRNA loci, and 109,724 SNPs that are located in predicted 7mer-m8 miRNA binding sites within porcine 3′UTR. In porcine miRNA genes, SNP density is reduced compared with their flanking non-miRNA regions. By sequencing the genomes of five Duroc boars, we identified 12 miRNA SNPs that were subsequently genotyped in their offspring (N = 345, Lipgen population). Association analyses of miRNA SNPs with 38 lipid-related traits and hepatic and muscle microarray expression phenotypes recorded in the Lipgen population were performed. The most relevant detected association was between the genotype of the rs319154814 (G/A) SNP located in the apical loop of the ssc-miR-326 hairpin precursor and PPP1CC mRNA levels in the liver (q-value = 0.058). This result was subsequently confirmed by qPCR (P-value = 0.027). The rs319154814 (G/A) genotype was also associated with several fatty acid composition traits.ConclusionsOur findings show a reduced variability of porcine miRNA genes, which is consistent with strong purifying selection, particularly in the seed region that plays a critical role in miRNA binding. Although it is generally assumed that SNPs mapping to the seed region are those with the most pronounced consequences on mRNA expression, we show that a SNP mapping to the apical region of ssc-miR-326 is significantly associated with hepatic mRNA levels of the PPP1CC gene, one of its predicted targets. Although experimental confirmation of such an interaction is reported in humans but not in pigs, this result highlights the need to further investigate the functional effects of miRNA polymorphisms that are located outside the seed region on gene expression in pigs.

Functional genetic variants in the 3'UTR of PTPRD associated with the risk of gestational diabetes mellitus.

A previous study revealed that protein tyrosine phosphatase receptor type D (PTPRD) is highly associated with diabetes mellitus, particularly for type 2 diabetes, through a genome-wide association study. However, the influence of the human polymorphism in the 3'-untranslated region (3'-UTR) of PTPRD on gestational diabetes mellitus (GDM) has remained to be defined. The present study focused on the functional polymorphism located in the 3'-UTR of PTPRD and whether it is associated with the susceptibility to develop GDM. A total of 1,100 pregnant female patients aged between 28 and 36 years within gestational weeks 24-28 were recruited. The participants enrolled in the study comprised 500 cases of GDM and 600 normal controls. Based on the screening results, the single nucleotide polymorphism (SNP) rs56407701 exhibited the most significant difference and may increase the susceptibility to GDM. A prediction of target microRNAs (miRNAs/miRs) using the miRNA SNP database indicated that SNP rs56407701 may be bound by miR-450a, causing the suppression of PTPRD expression in subjects with the GC or CC genotype. In conclusion, The CC genotype of PTPRD rs56407701, which may be bound by miR-450a, may increase the susceptibility of Chinese Han females to GDM during pregnancy. The present study provided a theoretical basis for the SNP rs56407701 being a source of GDM susceptibility loci.

The association between micro-RNA gene polymorphisms and the development of hepatocellular carcinoma in Egyptian patients.

IntroductionThe development and progression of hepatocellular carcinoma (HCC) is a multistage process involving the deregulation of genes that are crucial to cellular processes. Multiple risk factors are correlated with HCC. MicroRNA is differentially expressed in the development of different types of malignancies, including hepatic malignancy. Single nucleotide polymorphisms (SNPs) are the most common sequence variation in the human genome. SNPs in miRNAs may affect transcription, processing, or target recognition and result in malignant disease. The aim of the study was to determine the association between microRNA gene polymorphisms and the development of HCC in Egyptian patients.Material and methodsThis study included 200 individuals who were matched in age and sex. Tumour staging was done using the BCLC staging system. Quantification and genotyping of microRNA were performed.ResultsAmong the 200 patients, 2 groups were described: group I included 90 HCC patients with a male majority (72.2%), and group II comprised 110 controls. Three microRNA SNPs were assayed in both patients and controls. There was a significant association between rs10061133 miR-499b and the risk of HCC. The genotypes GG or G allele were significantly associated with an increased risk of HCC (GG: OR = 2.91, 95% CI: 1.23–4.22, p = 0.013; G allele: OR = 1.79, 95% CI: 1.12–2.15, p = 0.026) compared with the genotype of AA or AG or A allele.ConclusionsThere is an association between the miRNA SNPs and the susceptibility to HCC, to explore some roles and mechanisms of SNPs within miRNAs in the occurrence and development of HCC.

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.

The associations and roles of microRNA single-nucleotide polymorphisms in cervical cancer.

Cervical cancer is one of the fourth most common gynecological malignancies and has been identified as the fourth leading cause of cancer death in women worldwide. MicroRNAs (miRNAs) are single-stranded sequences of noncoding RNAs that are approximately 22-24 nucleotides in length. They modulate posttranscriptional mRNA expression and play critical roles in cervical cancer. Single nucleotide polymorphisms (SNPs) in miRNA genes may alter miRNA expression and maturation and have been associated with various cancers. This review mainly focuses on the roles of SNPs in miRNA genes in the development of cervical cancer and summarizes the research progress of miRNA SNPs in cervical cancer and their molecular regulation mechanisms.

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.

Genetic Variants in miRNAs Are Associated With Risk of Non-syndromic Tooth Agenesis.

Non-syndromic tooth agenesis (NSTA) is one of the most common dental abnormalities. MiRNAs participated in the craniofacial and tooth development. Therefore, single nucleotide polymorphisms (SNPs) in miRNA genes may contribute to the susceptibility of non-syndromic tooth agenesis. Here, a total of 625 non-syndromic tooth agenesis cases and 1,144 healthy controls were recruited, and four miRNA SNPs (miR-146a/rs2910164, miR-196a2/rs11614913, pre-miR-605/rs2043556, pre-miR-618/rs2682818) were genotyped by the TaqMan platform. Rs2043556 showed nominal associations with risk of non-syndromic tooth agenesis (PAdd = 0.021) in the overall analysis, as well as upper lateral incisor agenesis (PAdd = 0.047) and lower incisor agenesis (PAdd = 0.049) in the subgroup analysis. Notably, its significant association with upper canine agenesis was observed (PAdd = 0.0016). Rs2043556 affected the mature of miR-605-3p and miR-605-5p while dual-luciferase report analysis indicated that MDM2 was the binding target of miR-605-5p. Our study indicated that pre-miR-605 rs2043556 was associated with risk of non-syndromic tooth agenesis.

Associations of the microRNA gene polymorphisms with the risk of non-syndromic supernumerary teeth in a Chinese population

ObjectiveNon-syndromic supernumerary teeth (NSST) are a common type of dental anomaly. microRNAs (miRNAs) play an important role in craniofacial and tooth development. Therefore, we hypothesized that single nucleotide polymorphisms (SNPs) of miRNAs may be associated with the susceptibility of NSST. Materials and methodsFour miRNA SNPs (rs2910164, rs11614913, rs2043556, and rs2682818) were selected, and their associations with NSST susceptibility were evaluated in a case-control study (163 NSST patients and 326 healthy controls). Resultsrs2910164 was significantly associated with a risk of lower NSST (additive model: OR = 4.00, 95 % CI = 1.76–9.09, P = 0.001), and rs2682818 showed nominal association with a risk of upper NSST (additive model: OR = 1.40, 95 % CI = 1.02–1.91, P = 0.037) and NSST among male patients (additive model: OR = 1.62, 95 % CI = 1.08–2.43, P = 0.020). ConclusionGenetic variants of miR-146a/rs2910164 and miR-618/rs2682818 were likely associated with the risk of NSST in the Chinese population.

Genetic variations in MicroRNA genes and cancer risk: A field synopsis and meta-analysis.

Cancer risk has been associated with certain gene variations in microRNA (miRNA), but conflicting evidence warrants re-assessing of significant results in meta-analyses. We summarized published meta-analyses that assess the associations between miRNA polymorphism and cancers to show the validity of the findings. We searched PubMed and investigated the results of meta-analyses published through November 2018. We re-assessed the results based on false-positive report probability (FPRP) to test the noteworthiness of the associations. Sixty-eight miRNA polymorphisms in 45 meta-analyses associated with cancer were included. Four (7.4%) and sixteen (25.0%) single nucleotide polymorphisms(SNPs) were noteworthy (FPRP<0.2) at a prior probability of 0.001 for interesting candidate genes and a statistical power to detect an odds ratio (OR) of 1.1 and 1.5, respectively. The four miRNA SNPs noteworthy at an OR of 1.1 were as follows: miR-146a/rs2910164 Cvs.G; miR-27a/rs895819 Cvs.T; miR-423/rs6505162 Cvs.A; and miR-605/rs2043556 Cvs.T. The 16 SNPs noteworthy at an OR of 1.5 include the four genotype comparisons at an OR of 1.1, and the additional 12 genotype comparisons were as follows: miR-196a2/rs11614913 Tvs.C; miR-27a/rs895819 GGvs.AA+AG; miR-196a2/rs11614913 C vs.T; miR-146a/rs2910164 Gvs.C; miR-196a2/rs11614913 Tvs.C; miR-146a/rs2910164 Cvs.G; miR-499/rs3746444 homozygous model; miR-146a/rs2910164 CCvs.GG+GC; miR-499/rs3746444 TCvs.TT; miR-499/rs3746444 GAvs.AA; miR-146a/rs2910164 CCvs.GG; and miR-499/rs3746444 Gvs.A. No association was noteworthy at a prior probability of 0.000001. Out of 68 published associations of miRNA polymorphisms with cancer, sixteen have shown noteworthiness in our re-assessing meta-analysis. Our findings summarize the results of meta-analyses on the association of cancer with SNPs and underline the importance of interpreting results with caution.

Effects of microRNAs polymorphism in cancer progression.

MicroRNAs (miRNAs) are known as a new class of small RNAs (18-25 nucleotides) that regulate gene expression at multiple levels from transcription to translation. Considering the important role of miRNAs in cell proliferation, differentiation, and apoptosis, any variations in their expression can contribute to various anomalies, such as tumorigenesis. Single-nucleotide polymorphisms (SNPs) have received much attention as potential genetic markers for diseases due to their advantage of being present at a high frequency in the human genome. SNPs can occur in different parts of the miRNA genes (primary, precursor, and mature) which result in pathological conditions. In this study, recent findings related to the effects of SNPs in miRNAs on their biogenesis and functions and their role in cancer development and progression are discussed. This review was performed using PubMed to search for related reports. The identified effects may be useful for clinical decision-making and providing important new information about the pathophysiology of miRNAs.