miR-499 Rs3746444 Polymorphism Research Articles

Association between Mir-499, Mir-27a, and Mir-146a polymorphisms and their susceptibility to recurrent spontaneous abortion; in silico analysis.

Recurrent spontaneous abortion (RSA) is defined as two or more pregnancy losses before 24 gestational weeks, accounting for 1-3% of fertile couples. A vast majority of single-nucleotide polymorphisms (SNPs) in some microRNA (miRNA) genes can change the miRNA-mRNA interaction and are associated with the risk of RSA. This study was designed to better elucidate the association between miR-27a, miR-499, and miR-146a polymorphisms and RSA risk. SNP genotyping of miR-27a (rs895819), miR-499 (rs3746444), and miR-146a (rs2910164) was performed using polymerase chain reaction (PCR)-restriction fragment length polymorphism and tetra amplification-refractory mutation system PCR in 98 patients with RSA and 105 healthy subjects. Our results showed that the miR-499 rs3746444 and miR-27a rs895819 polymorphisms were significantly associated with RSA risk, whereas no significant differences were observed between the rs2910164 polymorphism and RSA susceptibility. We proposed that the miR-499 rs3746444 and miR-27a rs895819 polymorphisms were correlated with RSA in our population, but the miR-146a rs2910164 variant was not associated with the risk of RSA.

Association between Susceptibility to Systemic Lupus Erythematous and Polymorphisms in miR-146a and miR-499: A Meta-Analysis

Introduction: This study aimed to determine whether miR-146a and miR-499 polymorphisms are associated with susceptibility to systemic lupus erythematosus (SLE). Methods: We searched the MEDLINE, EMBASE, and Cochrane databases. We performed a meta-analysis on the association of miR-146a rs2910164, rs2431697, rs57095329, and miR-499 rs3746444 polymorphisms with susceptibility to SLE. Results: Twenty-one studies from 17 reports, with 18,910 patients and 29,622 controls, were included in the meta-analysis. Meta-analysis revealed no association between SLE and the rs2910164 C allele (odds ratio [OR] = 0.999, 95% confidence interval [CI] = 0.816–1.222, p = 0.990). Stratification by ethnicity indicated no association between the miR-146a C allele and SLE in Arab or Latin American populations. The meta-analysis revealed an association between SLE and the miR-499 rs374644 CC + CT genotype in the overall group (OR = 1.313, 95% CI = 1.015–1.698, p = 0.038). Furthermore, meta-analysis revealed a significant association between SLE and the miR-146a rs2431697 C allele in the overall group (OR = 0.746, 95% CI = 0.697–0.798, p = 0.038). The miR-146a rs2431697 C allele is protective against SLE risk. Stratification by ethnicity indicated an association between the miR-146a rs2431697 C allele and SLE in Asian and European, but not Arab populations. The meta-analysis showed an association between the miR-146a rs57095329 G allele and SLE in Asian, but not Arab populations. Discussion/Conclusion: This meta-analysis suggests that the miR-146a rs2431697 polymorphism is a protective factor against the risk of SLE, and that the miR-146a rs57095329 and miR-499 rs3746444 polymorphisms are associated with susceptibility to SLE. However, miR-146a rs2910164 was not associated with susceptibility to SLE.

Association of miR-499 Polymorphism and Its Regulatory Networks with Hashimoto Thyroiditis Susceptibility: A Population-Based Case-Control Study.

Hashimoto thyroiditis (HT) is a common autoimmune disorder with a strong genetic background. Several genetic factors have been suggested, yet numerous genetic contributors remain to be fully understood in HT pathogenesis. MicroRNAs (miRs) are gene expression regulators critically involved in biological processes, of which polymorphisms can alter their function, leading to pathologic conditions, including autoimmune diseases. We examined whether miR-499 rs3746444 polymorphism is associated with susceptibility to HT in an Iranian subpopulation. Furthermore, we investigated the potential interacting regulatory network of the miR-499. This case-control study included 150 HT patients and 152 healthy subjects. Genotyping of rs3746444 was performed by the PCR-RFLP method. Also, target genomic sites of the polymorphism were predicted using bioinformatics. Our results showed that miR-499 rs3746444 was positively associated with HT risk in heterozygous (OR = 3.32, 95%CI = 2.00–5.53, p < 0.001, CT vs. TT), homozygous (OR = 2.81, 95%CI = 1.30–6.10, p = 0.014, CC vs. TT), dominant (OR = 3.22, 95%CI = 1.97–5.25, p < 0.001, CT + CC vs. TT), overdominant (OR = 2.57, 95%CI = 1.62–4.09, p < 0.001, CC + TT vs. CT), and allelic (OR = 1.92, 95%CI = 1.37–2.69, p < 0.001, C vs. T) models. Mapping predicted target genes of miR-499 on tissue-specific-, co-expression-, and miR-TF networks indicated that main hub-driver nodes are implicated in regulating immune system functions, including immunorecognition and complement activity. We demonstrated that miR-499 rs3746444 is linked to HT susceptibility in our population. However, predicted regulatory networks revealed that this polymorphism is contributing to the regulation of immune system pathways.

The correlation of microRNA-499 rs3746444 T>C locus with the susceptibility of gastric cancer: from a case-control study to a meta-analysis.

The relationship between rs3746444 T>C single-nucleotide polymorphism (SNP) in microRNA (mir)-499 and risk of gastric cancer (GC) has been widely investigated. However, the association was still unconfirmed. Here, we first recruited 490 GC patients and 1476 controls, and conducted a case-control study. And we did not find any association between rs3746444 T>C SNP polymorphism and risk of GC. Subsequently, we conducted a meta-analysis to explore the association of mir-499 rs3746444 polymorphism with GC development. Two authors searched the PubMed and EMBASE databases up to October 15, 2019 independently. Finally, nine literatures involving 12 independent studies were included. In total, 3954 GC cases and 9745 controls were recruited for meta-analysis. The results suggested that allele model, homozygote model and recessive model could increase the risk of overall GC (P = 0.002, 0.009 and 0.013, respectively). When we excluded the studies violated HWE, this association was also found in allele model (P = 0.020) and dominant model (P= 0.044). In subgroup analyses, we identified that rs3746444 SNP in mir-499 increased the risk of GC in Asians and gastric cardiac adenocarcinoma (GCA) subgroups. No significant bias of selection was found (all P>0.1). Test of sensitivity analysis indicated that our findings were stable. Additionally, we found that the power value was 0.891 in the allele model, suggesting the reliability of our findings. In summary, our analysis confirmed the association between rs3746444 and the risk of GC, especially in Asians and in patients with GCA.

Expression of MiR-608 in Nonsmall Cell Lung Cancer and Molecular Mechanism of Apoptosis and Migration of A549 Cells.

Objective This Work is aimed at exploring the effect of microRNA (MiR)-608 on the function of nonsmall cell lung cancer (NSCLC) A549 cells and related mechanisms. Methods Blood samples of 106 NSCLC patients (experimental group) as well as 124 normal people (control group) were selected for relevant investigation. Polymerase chain reaction (PCR) as well as DNA sequencing was used to determine the genotyping of the MiR-608 rs4919510 polymorphism. MiR-608 expression in cells was detected by real-time PCR technology. Western blotting was used to detect changes in protein levels. NSCLC tissues as well as adjacent tissues were explored in 33 patients undergoing surgery. Results MiR-608 rs4919510 does not influence the incidence of NSCLC patients. In addition, MiR-608 expression was downregulated in the tumor tissue of NSCLC patients, while the transcription factor activating enhancer-binding protein 4 (TFAP4) expression was upregulated. MiR-608 promotes DOX- (Doxorubicin-) induced apoptosis by negatively regulating TFAP4 expression in NSCLC tissue. TFAP4 can significantly inhibit the migration of A549 cells. Conclusion The findings in this investigation can contribute to the effective treatment of NSCLC patients. Also, the investigation can provide some theoretical support for the application of new targets for NSCLC treatment.

MiR-608 rs4919510 Polymorphism May Affect Susceptibility to Colorectal Cancer by Upregulating MRPL43 Expression.

There are many studies on the association between miR-608 rs4919510 polymorphism and susceptibility to colorectal cancer (CRC). However, the role of rs4919510 in CRC development and its underlying mechanism remain unclear. We first evaluated the gene that may be regulated by the variation of rs4919510 through a two-stage expression quantitative trait loci analysis and then compared the expression of that identified gene in CRC tissues and adjacent nontumor tissues. Next, methyl thiazolyl tetrazolium (MTT) assay, transwell assay, and flow cytometry analyses were performed to investigate the in vitro capacity of cell proliferation, migration, invasion, apoptosis, and cell cycle of CRC cells, respectively. Finally, through bioinformatics prediction, we contrasted the regulatory network and identified microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) that could regulate the obtained gene. We found that the variant G allele of rs4919510 located in miR-608 was associated with a potentially increased expression of MRPL43 in colon tissues (p = 0.065). Moreover, the results of functional experiments suggested that knockdown of the MRPL43 gene could inhibit the growth of the CRC HCT-116 cell line and promote apoptosis. Additionally, the cell cycle of CRC HCT-116 cell line was significantly arrested at the G2 phase. Next, we obtained a competing endogenous RNA regulatory network of MRPL43 with 17 pairs of miRNAs-lncRNAs by bioinformatics prediction, out of which, survival analysis indicated that different expression levels of miR-193b-3p (p = 0.0269) and miR-194-3p (p = 0.0113) were associated with overall survival in CRC patients. The rs4919510 variant G allele in miR-608 may increase the proliferation, invasion, and migration ability and decrease the apoptosis of CRC HCT-116 cell line by upregulating the expression of MRPL43, ultimately may affect the risk of CRC. Moreover, miR-193b-3p and miR-194-3p that target MRPL43 may serve as potential predictive biomarkers of CRC survival.

Association of two polymorphisms of miRNA-146a rs2910164 (G > C) and miRNA-499 rs3746444 (T > C) with asthma: a meta-analysis

Objective To conduct a meta-analysis to determine the association between two single nucleotide polymorphisms (SNPs) miRNA146a rs2910164 (G > C) and miRNA-499 rs3746444 (T > C) and asthma risk. Data Sources PubMed and Embase (updated May 17, 2019). Keywords (microRNA OR microRNAs) AND (polymorphism OR polymorphisms) AND (Asthmas OR Bronchial Asthma OR Asthma, Bronchial). Results Six eligible case-control studies (2441 asthma cases and 3044 controls) met our inclusion criteria. A trend of increased asthma risk was indicated by the heterozygote model (miR-499: TC versus TT, OR = 1.38, 95% CI = 1.06–1.79, P < 0.01) and the dominant model (miR-499: TC + CC versus TT, OR = 1.60, 95% CI = 1.07–2.39, P < 0.01) of miRNA-499 rs3746444. Polymorphisms rs2910164 in miRNA-146a of the allele model (miR-146a: C versus G, OR = 0.84, 95% CI = 0.74–0.96, P = 0.238), homozygote model (miR-146a: CC versus GG, OR = 0.68, 95% CI = 0.51–0.91, P = 0.213), recessive model (miR-146a: CC versus GC + GG, OR = 0.75, 95% CI = 0.60–0.94, P = 0.149) indicated a decreased risk of asthma. Conclusions The miR-499 rs3746444 (T > C) polymorphism is associated with asthma susceptibility and miRNA-146a rs2910164 (G > C) polymorphism has a protective role against susceptibility to asthma.

MicroRNA-499 rs3746444 polymorphism in Egyptian children with biliary atresia.

Aim of the studyWe aimed to evaluate the association of microRNA-499 rs3746444 polymorphism and biliary atresia (BA) risk and its correlation with clinic-pathologic features of BA.Material and methodsThis study was performed on 300 Egyptian children (100 BA cases, 100 cases with cholestatic liver diseases other than BA and 100 healthy controls). Routine laboratory investigations, clinical examination and abdominal ultrasound were done. All infants were genotyped for miR-499 single nucleotide polymorphisms (SNPs) (rs3746444 A>G) by real-time polymerase chain reaction (PCR) fluorescence detection on a Rotor Gene Real Time PCR System (QIAGEN, GmbH) using fluorescent labeled probes.ResultsThe AG genotype was the most prevalent genotype of miR-499 rs3746444 among the studied groups. A significantly higher frequency of the rs3746444 G allele was found in the BA cases than the other groups (odds ratio = 1.62). This polymorphism was also correlated with the degree of fibrosis in BA cases (p < 0.05). The miR-499 rs3746444 polymorphism (GG genotype) was significantly associated with severe form of BA and bad prognosis after the Kasai operation (p < 0.05). miR-499 rs3746444 polymorphism had no effect on the clinic-pathological features or the liver function status in the non-BA group.ConclusionsThere is an association between the miR-499 SNP genotypes and the occurrence of BA. The variant allele G is the predominant allele in the BA group and is associated with severe liver inflammation and bad prognosis after the Kasai operation.

Association between miR-499 rs3746444 polymorphism and coronary heart disease susceptibility: An evidence-based meta-analysis of 5063 cases and 4603 controls

MicroRNA-499 (miR-499) rs3746444 polymorphism has been associated with the risk of coronary heart disease (CHD). However, results from several studies are inconsistent. This meta-analysis aimed to further investigate the possible association between miR-499 rs3746444 polymorphism and CHD risk. A total of 9 case-control studies included 5063 CHD cases and 4603 healthy subjects. The A allele at rs374644 was associated with significantly decreased CHD risk in the total population according to the allelic model (OR = 0.80, 95% CI = 0.68–0.93, P = 0.005), homozygous model (OR = 0.52, 95% CI = 0.39–0.71, P < 0.001) and heterozygous model (OR = 0.57, 95% CI = 0.43–0.77, P < 0.001). A similar trend was found specifically in Asian and Chinese populations. In contrast, the wild-type GG genotype at rs374644 was associated with significantly increased CHD risk in the total population, according to the dominant model (OR = 1.83, 95% CI = 1.39–2.42, P < 0.001), and a similar trend was found in Asian and Chinese populations. These results indicate that in the total population, as well as in Asian and Chinese populations, the wild-type GG genotype at rs374644 may be related to increased susceptibility to CHD, while the A allele may be protective against CHD.

Association between polymorphisms in microRNAs and ischemic stroke in an Asian population: evidence based on 6,083 cases and 7,248 controls.

BackgroundPolymorphisms in miR-146a (rs2910164), miR-196a2 (rs11614913), miR-149 (rs2292832) and miR-499 (rs3746444) have been associated with ischemic stroke (IS), but studies have given inconsistent results.MethodsThis meta-analysis investigated the possible association between IS risk and the four polymorphisms. A total of 14 case-control studies from Asian populations involving 6,083 cases and 7,248 controls for the four polymorphisms were included.ResultsResults showed that the GG genotype of miR-146a (rs2910164) may be associated with increased IS risk according to the recessive model (OR=1.20, 95% CI=1.02–1.42, P=0.03). Similarly, the CC genotype of miR-149 (rs2292832) may be associated with increased IS risk according to the recessive model (OR=1.28, 95% CI=1.08–1.52, P=0.005) and the homozygous model (OR=1.31, 95% CI=1.09–1.58, P=0.004). In contrast, miR-196a2 (rs11614913) and miR-499 (rs3746444) polymorphisms did not show significant association with IS risk in any of the five genetic models.ConclusionThese results indicate that the GG genotype of miR-146a (rs2910164) and CC genotype of miR-149 (rs2292832) may confer increased susceptibility to IS, while miR-196a2 (rs11614913) and miR-499 (rs3746444) polymorphisms may not be associated with IS risk in Asian populations. These conclusions should be verified in large and well-designed studies.

MiR-499 rs3746444 polymorphism and hepatocellular carcinoma risk

Several studies suggested that miR-499 rs3746444 polymorphism was associated with the risk of hepatocellular carcinoma (HCC). However, other studies did not confirm the result. To derive a more comprehensive estimation of the association between miR-499 rs3746444 polymorphism and HCC risk, we conducted a meta-analysis. PUBMED, COCHRANE, and WEB OF SCIENCE databases were retrieved for the association studies focused on the relationship between miR-499 rs3746444 polymorphism and the risk of HCC. The strength of the associations between miR-499 rs3746444 polymorphism and the risk of HCC was measured by odds ratios (ORs) with 95% confidence intervals (CIs). A statistically significant association between miR-499 rs3746444 polymorphism and the risk of HCC was fond (OR = 1.26; 95% CI, 1.04-1.52; P = 0.02). In the subgroup analysis of race, Asian population with miR-499 rs3746444 polymorphism showed increased HCC risk (OR = 1.29; 95% CI, 1.03-1.62; P = 0.03). In the subgroup analysis of hepatitis virus status, patients with HBV and miR-499 rs3746444 polymorphism showed increased HCC risk (OR = 1.38; 95% CI, 1.17-1.64; P = 0.0002). In the subgroup analysis of source of control, both hospital- and population-based studies found significant results (OR = 1.46; 95% CI, 1.12-1.90; P = 0.005; OR = 1.19; 95% CI, 1.01-1.40; P = 0.04). This meta-analysis suggested that mir-499 rs3746444 polymorphism was associated with an increased HCC risk.

Association of single nucleotide polymorphisms in miR- 499 and miR-196a with susceptibility to breast cancer

Purpose: To investigate the relationship between miR-499 rs3746444 and miR-196a rs11614913 polymorphisms, and susceptibility to breast cancer in an Iranian population. Methods: This case-control study was performed on a population of 200 subjects comprising 100 breast cancer patients (case/observation group) and 100 healthy individuals (control group). Amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) was used to genotype these polymorphisms. P-values and odd ratios were determined, and p-values 1 were considered statistically significant. Results: There were no significant differences between observation and control groups with respect to rs11614913 T/C polymorphism. The rs11614913 T allele was not identified as a risk factor for susceptibility to breast cancer (OR = 0.86, 95 % CI = 0.85 - 1.3, p = 0.46). However, there were significant differences between observation and control groups with respect to rs3746444 T/C polymorphism. It was observed that cytosine-cytosine (CC) (OR = 4.5, 95 % CI = 1.3 - 15.4, p = 0.06), and cytosine-thymine (CT) (OR = 1.9, 95% CI = 1- 3.6, p = 0.04) genotypes had protective influence against susceptibility to breast cancer. Conclusion: These results indicate that CC and CT genotypes are associated with reduced risk of breast cancer. In particular, the presence of C allele is significantly associated with a low risk of breast cancer. These findings may provide useful information for prevention and early diagnosis of breast cancer. Keywords: Breast cancer, Early diagnosis, miR-196a rs11614913, miR-499 rs3746444, Polymorphism, ARMS-PCR

Association of miR-196a2 rs11614913 and miR-499 rs3746444 polymorphisms with cancer risk: a meta-analysis.

BackgroundMicroRNAs (miRNAs) are small non-coding RNA molecules, which participate in diverse biological processes and may regulate tumor suppressor genes or oncogenes. Rs11614913 in miR-196a2 and rs3746444 in miR-499 are shown to associate with increased/decreased cancer risk. This meta-analysis was performed to systematically assess the overall association.Materials and MethodsWe searched Pubmed, Web of Knowledge, EMBASE, Chinese National Knowledge Infrastructure (CNKI) databases until December 2016 to identify eligible studies. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the strength of the associations.ResultsWe assessed published studies of the association between these microRNA polymorphisms and cancer risk from 56 studies with 21958/26436 cases/controls for miR-196a2 and from 37 studies with 13759/17946 cases/controls for miR-499. The results demonstrated that miR-196a2 rs11614913 was significantly associated with a decreased cancer risk, in particular with a decreased risk for colorectal cancer and gastric cancer, or for Asian population subgroup. In addition, miR-499 rs3746444 polymorphism was observed as a risk factor for cancers, in particular, for breast cancer, or for in the Asian population.ConclusionsOur meta-analysis suggests that the rs11614913 most likely contributes to decreased susceptibility to cancer, especially in Asians and colorectal cancer and gastric cancer, and that the rs3746444 may increase risk for cancer. Furthermore, more well-designed studies with large sample size are still necessary to further elucidate the association between polymorphisms and different kinds of cancers risk.

Two single nucleotide polymorphisms within corresponding microRNAs and tuberculosis risk: A meta-analysis

BackgroundsPrevious studies suggest that miR-146a rs2910164 and miR-499 rs3746444 polymorphisms are associated with susceptibility to pulmonary tuberculosis, but the reported findings are inconsistent. We conducted this meta-analysis to evaluate the relationships between the two single nucleotide polymorphisms and tuberculosis. MethodsPotentially relevant studies were identified by searching PubMed and Embase databases in addition to manual searches of references of retrieved full publications. The summary odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a random-effect model. ResultsA total of 4 reports containing 5 independent studies were included in this meta-analysis. Neither miR-146a rs2910164 polymorphism nor miR-499 rs3746444 polymorphism was found to be associated with pulmonary tuberculosis. Studies with different ethnicities are needed to confirm our findings. ConclusionsThis meta-analysis suggests that miR-146a rs2910164 polymorphism and miR-499 rs3746444 polymorphism are not associated with pulmonary tuberculosis.

A meta-analysis: Is there any association between MiR-608 rs4919510 polymorphism and breast cancer risks?

ObjectTo combine the data from previously conducted studies about the associations between miR-608 rs4919510 polymorphism (C>G) and breast cancer risks.MethodsAccording to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a systematic review of the related literatures searched from PubMed, Embase, Cochrane Library, Web of Science, and China National Knowledge Internet (CNKI) (time: ~ December 2016). Using DerSimonian-Laird random-effects models [Pooling Model: Mantel Haenszel (MH)], odd ratios (ORs) with 95% confidence intervals (95% CIs) were estimated in the allele model, homozygote model, heterozygote model, dominant model and recessive model. Heterogeneity was analyzed using Labbr plots and I2 statistic. Publication bias was analyzed using contour-enhanced funnel plots.ResultsWe included 5 eligible studies with 7948 patients. The ORs and their 95% CIs in the 5 genetic models mentioned above were 1.009 (95% CI: 0.922, 1.104; p = 0.847), 1.098 (95% CI: 0.954, 1.264; p = 0.194), 1.076 (95% CI: 0.956, 1.211; p = 0.227), 1.043 (95% CI: 0.880, 1.236; p = 0.628), 1.007 (95% CI: 0.906, 1.118; p = 0.899), respectively.ConclusionIn the present meta-analysis, no relationships between miR-608 rs4919510 polymorphism (C>G) and the risk of breast cancer were found. More studies are warranted to further validate the conclusion.

Functional polymorphisms in pre-miR146a and pre-miR499 are associated with systemic lupus erythematosus but not with rheumatoid arthritis or Graves' disease in Mexican patients.

Recently, different microRNA (miRNA) gene polymorphisms have been evaluated in patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Graves’ disease (GD). In the present study, we examined three single-nucleotide polymorphisms (SNPs) located in the pre-miR-146a (rs2910164G/C), pre-miR-196a-2 (rs11614913C/T), and pre-miR-499 (rs3746444A/G) genes. Our study population included 900 Mexican patients with RA, SLE, or GD, as well as 486 healthy control individuals with no family history of inflammatory or autoimmune diseases. Genotyping was performed using TaqMan probes and a 5′ exonuclease assay. None of the investigated SNPs were associated with RA or GD susceptibility under any genetic model (co-dominant, recessive, or dominant). Genotype and allele frequencies of the miR-196a-2 rs11614913C/T polymorphism were similar between SLE cases and controls. In contrast, the miR-146a rs2910164G/C and miR-499 rs3746444A/G polymorphisms were associated with SLE susceptibility. These SNPs were not associated with lupus nephritis (LN). Our results suggest that polymorphisms in miR-146a, miR-196a-2, and miR-499 are not associated with RA or GD susceptibility. This is the first report documenting that the miR-146a rs2910164G/C and miR-499 rs3746444 polymorphisms are associated with SLE susceptibility but not with LN.

Association between polymorphisms in pre-miRNA genes and risk of oral squamous cell cancer in a Chinese population.

BackgroundMicroRNAs play important roles in the development of human cancers. This case-control study is to evaluate the roles of the polymorphisms in pre-miRNAs on risk of oral cancer in a Chinese population.MethodsThe genotypes of three polymorphisms were determined in 340 patients with oral squamous cell cancer and 340 healthy controls who were frequency matched for age and sex. Odds ratios (ORs) and 95% confidence intervals (95%CIs) were calculated to assess the association. All analyses were performed using the SPSS software. 3.154() 0.001.ResultsFor miR-499 rs3746444, individuals carrying homozygous CC genotype had increased risks of oral cancer compared with the homozygous wild TT genotype (adjusted OR was 3.154, 95%CI was 1.555–6.397, P value was 0.001). The C allele of miR-499 rs3746444 was associated with a higher risk of oral cancer with significant odds ratio of 1.453. In the stratified analyses by sex, the associations between miR-499 rs3746444 and miR-146a rs2910164 polymorphisms with the susceptibility of oral squamous cell cancer were significant in males. However, with 1/4 as many subjects there were no significant associations between the three polymorphisms and oral cancer risks in females. The joint effects of miRNA polymorphisms and smoking on the risk of OSCC were analyzed and the results suggested that the association between microRNA genetic variants and OSCC risk was modified by smoking.ConclusionsThese findings suggest that miR-499 rs3746444 and miR-146a rs2910164 polymorphisms may contribute to genetic susceptibility to oral squamous cell cancer.

The miR-608 rs4919510 polymorphism may modify cancer susceptibility based on type.

Previous meta-analysis has not shown different effects of miR-608 rs4919510 polymorphism in specific cancer types and reported no significant association between rs4919510 and cancer risk among Chinese. However, more recent findings have been inconsistent. Therefore, we performed an updated meta-analysis to examine whether this polymorphism is associated with cancer risk based on ethnicity and type. A total of 18 case-control studies, comprising 12,517 cases and 15,624 controls, were included in our study. Surprisingly, in contrast with previous meta-analysis, a significant association between the rs4919510 polymorphism and cancer risk was observed in Chinese (CG vs CC: odds ratio = 1.11; 95% confidence interval = 1.04-1.19). In further stratified analyses based on cancer type, rs4919510 was significantly associated with an increased risk of papillary thyroid cancer (CG vs CC: odds ratio = 1.25; 95% confidence interval = 1.01-1.54) and exhibited borderline significant associations with increased risk of gastric cancer (GG vs CC: odds ratio = 1.27; 95% confidence interval = 1.00-1.62) and lung cancer (CG vs CC: odds ratio = 1.14; 95% confidence interval = 0.99-1.32), but a decreased risk of colorectal cancer (GG vs CC: odds ratio = 0.74; 95% confidence interval = 0.60-0.91). Moreover, the RegulomeDB database indicated that rs4919510 may affect the expression of two nearby genes ( SEMA4G and MRPL43), and the Cancer Genome Atlas database revealed that the expression level of SEMA4G was significantly lower in colorectal cancer and lung cancer tissues than that in adjacent non-tumour tissues, while the expression level of SEMA4G was significantly higher in gastric cancer tissues than that in adjacent non-tumour tissues. These findings provide evidence that the miR-608 rs4919510 polymorphism may modify cancer susceptibility in a type-specific manner. Furthermore, SEMA4G may function as an oncogene or tumour suppressor to regulate tumour development in a type-specific manner. Further studies with experimental evaluations are warranted.

Pre-micro RNA-499 Gene Polymorphism rs3746444 T/C is Associated with Susceptibility to Rheumatoid Arthritis in Egyptian Population

Pre-miRNA-499 gene is associated with autoimmune disease. Mir-449 rs3746444 polymorphism is inconsistent for rheumatoid arthritis (RA). This study aimed to investigate association of mir-499 rs3746444 polymorphism with RA activity and severity in Egyptian population. The study population was conducted as case control study in 100 RA patients diagnosed according to the American College of Rheumatology classification criteria for RA, and the control group included 100 healthy subjects who were age-and sex-matched to the RA group. Different genotypes were assessed using polymerase chain reaction-restriction fragment length polymorphism. 95% Confidence interval and odds ratio were defined to assess the strength of association. Regarding patients, thirty-three patients carried TT genotype, fifty-three patients carried TC genotype and fourteen patients carried CC genotype. So the frequency of the minor C allele in RA patients was significantly higher than the control subjects (P=0.037). TC, CC genotypes and C allele frequencies were significantly associated with disease severity as they had high rheumatoid factor (55.78 µIU/ml) and anti-cyclic citrullinated peptide (Anti-CCP) antibody (297.32 µIU/ml). Moreover, the heterozygote TC had more severe and more active form of the disease compared with homozygote CC or TT as they had high Anti-CCP antibody, and disease activity score 28 (score 5). Our work suggests that C allele of Pre-miRNA rs3746444 polymorphism contributes to heritability of susceptibility to RA compared to T allele. This polymorphism was associated with the activity and severity of the disease.

Study of the association between five polymorphisms and risk of hepatocellular carcinoma: A meta-analysis

BackgroundRecently, several studies have investigated the association between polymorphisms in miR-146a rs2910164, miR-196a2 rs11614913, miR-499 rs3746444, miR-149 rs229283, miR-34b/c rs4938723, and hepatocellular carcinoma (HCC), which showed inconclusive results. MethodsA publication search was performed in PubMed, ExcerptaMedica Database, Chinese Biomedical Literature Database, and Chinese National Knowledge Infrastructure to collect relevant medical data published through February 2016. The aim of this study was to ascertain the association between HCC and micro-RNAs. A total of 21 studies were included in our study, which showed that miR-146a rs2910164 polymorphism has a significant association with HCC in the allele, recessive, and homozygous models overall [allele model: odds ratio (OR) = 0.927, 95% confidence interval (CI): 0.869–0.988, p = 0.02; recessive model: OR = 0.893, 95% CI: 0.814–0.981, p = 0.018; homozygous model: OR = 0.853, 95% CI: 0.744–0.978, p = 0.023] and in Asian populations (allele model: OR = 0.921, 95% CI: 0.863–0.983, p = 0.014; recessive model: OR = 0.893, 95% CI: 0.814–0.981, p = 0.019; homozygous model: OR = 0.851, 95% CI: 0.741–0.977, p = 0.022). For miR-196a2 rs11614913, significant statistical heterogeneity overall and in Asian populations was identified in the comparison of the allele, recessive, homozygous, and heterozygous models (overall: allele model: OR = 0.889, 95% CI: 0.842–0.94, p < 0.001; recessive model: OR = 0.837, 95% CI: 0.723–0.970, p = 0.018; homozygous model: OR = 0.722, 95%CI: 0.575–0.906, p = 0.005; heterozygous model: OR = 0.532, 95% CI: 0.37–0.765, p = 0.001), and also has a decreased risk of HCC in Caucasians in all genetic models except for the heterozygous model (allele model: OR = 0.658, 95% CI: 0.49–0.885, p = 0.006; dominant model: OR = 0.641, 95% CI: 0.418–0.981, p = 0.041; recessive model: OR = 0.489, 95% CI: 0.278–0.862, p = 0.013; homozygous model: OR = 0.414, 95% CI: 0.222–0.772, p = 0.005). Only the recessive models produced a significant association between miR-499 rs3746444 polymorphism and HCC risk (recessive model: OR = 1.283, 95% CI: 1.008–1.632, p = 0.043). ResultsThe analysis for miR-146a rs2910164 polymorphisms by racial decent found the same association between miR-146a rs2910164 polymorphism and susceptibility to HCC in Asians, but no significance risk association was observed in Caucasians. The meta-analysis results showed that miR-196a2 rs11614913 was associated with a decreased risk of HCC in Caucasians in all genetic models except for the heterozygous model. In the Asian population, miR-499 rs3746444 polymorphism was associated with a decreased risk of HCC in recessive models. This meta-analysis showed that no significant statistical heterogeneity was identified in miR-149 rs2292832 and miR-34b/c rs4938723. ConclusionOur findings supported the proposition that the polymorphisms of miR-146a rs2910164, miR-196a2 rs11614913, and miR-196a2 rs11614913 may contribute to the susceptibility of HCC.