miR-146a Single Nucleotide Polymorphisms Research Articles

Association of single nucleotide polymorphism miRNA-146a (rs2910164) with increased predisposition to oral squamous cell carcinoma in central India population.

miRNAs play a crucial role in the genesis of cancer, either as tumor suppressor genes or as oncogenes. Single Nucleotide Polymorphisms (SNPs) in the seed region of microRNAs (miRNAs) can dysregulate their levels in the tissues and thereby affect carcinogenesis. The association of SNP in miR-146a (rs2910164) with the risk of oral squamous cell carcinoma (OSCC) has not been understood. In the present study, we have determined the association and functional significance of miR-146a (rs2910164) SNP with susceptibility to OSCC predisposition. In the present case-control study, we enrolled 430 subjects from central India (215 OSCC cases and 215 healthy controls). We performed genotyping by Kompetitive Allele Specific PCR (KASP), and their correlation with OSCC susceptibility was analyzed. miRNA expression profiling in tumor tissues and adjacent normal tissues from six OSCC patients was done by a NanoString n-Counter-based assay. Subsequently, gene ontology and pathway analysis were performed with FunRich version 3.13. The CC genotype of rs2910164 miR-146a was significantly associated with the increased risk for OSCC (CC vs GC, OR = 2.62; 95% CI: 1.48-4.66; p value = 0.001). However, the GC genotype was protective with GC vs CC (OR = 0.38, 95%CI =0.21-0.67, p-value = 0.001), and GC vs GG (OR = 0.58, 95%CI = 0.37-0.89, p-value = 0.01). Our finding suggests that SNP rs2910164 of miR-146a may be a genetic risk factor for OSCC susceptibility in the Central India population. However, more extensive multicenter studies are required to validate these findings.

Association Analysis Between the Functional Single Nucleotide Variants in miR-146a, miR-196a-2, miR-499a, and miR-612 With Acute Lymphoblastic Leukemia.

BackgroundAcute lymphoblastic leukemia (ALL) is characterized by an abnormal proliferation of immature lymphocytes, in whose development involves both environmental and genetic factors. It is well known that single nucleotide polymorphisms (SNPs) in coding and noncoding genes contribute to the susceptibility to ALL. This study aims to determine whether SNPs in miR-146a, miR-196a-2, miR-499a, and miR-612 genes are associated with the risk to ALL in pediatric Mexican population.MethodsA multicenter case-control study was carried out including patients with de novo diagnosis of ALL and healthy subjects as control group. The DNA samples were obtained from saliva and peripheral blood, and the genotyping of rs2910164, rs12803915, rs11614913, and rs3746444 was performed using the 5′exonuclease technique. Gene-gene interaction was evaluated by the multifactor dimensionality reduction (MDR) software.Results miR-499a rs3746444 showed significant differences among cases and controls. The rs3746444G allele was found as a risk factor to ALL (OR, 1.6 [95% CI, 1.05–2.5]; p = 0.028). The homozygous GG genotype of rs3746444 confers higher risk to ALL than the AA genotype (OR, 5.3 [95% CI, 1.23–23.4]; p = 0.01). Moreover, GG genotype highly increases the risk to ALL in male group (OR, 17.6 [95% CI, 1.04–298.9]; p = 0.00393). In addition, an association in a gender-dependent manner among SNPs located in miR-146a and miR-196a-2 genes and ALL susceptibility was found.ConclusionOur findings suggest that SNP located in miR-499a, miR-146a, and miR-196a-2 genes confer risk to ALL in Mexican children. Experimental analysis to decipher the role of these SNPs in human hematopoiesis could improve our understanding of the molecular mechanism underlying the development of ALL.

An association study between FokI, BsmI, miR-146a, and miR-155 and Behcet\u2019s disease in the Egyptian population

BackgroundBehcet’s disease (BD) is a systemic inflammatory disease of the blood vessels and affects various body parts. This study aimed to determine the association of four single-nucleotide polymorphisms (SNPs) and BD in the Egyptian population using multiple statistical models and show the resulting associations along with previous studies of different populations. Four SNPs were examined for their association with BD: two SNPs from vitamin D receptor gene (FokI and BsmI) were selected and the other two were selected from miR-146a and miR-155. These four SNPs were selected for their association and role with BD in different populations and in the immune system. A marker check was conducted using the Hardy-Weinberg equilibrium and minor allele frequency. The associations were tested using four different statistical models: multiplicative, dominant, recessive, and codominant models. All statistical models used the odd’s ratio (OR) with confidence interval (CI) of 95% to evaluate the association of each SNP.ResultsBsmI showed association using the four models, while FokI did not show any association through any model. miR-155 showed association using the multiplicative and recessive models. miR-146a showed association using the multiplicative model only.ConclusionsAs a result, BsmI, miR-155, and miR-146a SNPs could have a role in the development of BD in the Egyptian population, while FokI could have a weak role, if any, in the development of BD in the Egyptian population.

The miR-146a SNP Rs2910164 and miR-155 SNP rs767649 Are Risk Factors for Non-Small Cell Lung Cancer in the Iranian Population.

Background Lung cancer is one of the leading causes of death worldwide. MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression and may act as both tumor suppressors and as oncogenes. The presence of single nucleotide polymorphisms (SNPs) inside the miRNA genomic region could affect target miRNA maturation, expression, and binding to its target mRNA and contribute to cancer development. Previous studies on the SNPs Rs2910164 in miR-146a and Rs767649 in miR-155 showed association with non-small cell lung cancer (NSCLC) development. Thus, the aim of this study was to detect any correlation between those SNPs in Iranian NSCLC patients. Methods In a small cohort study, 165 NSCLC patients and 147 noncancer controls were enrolled between Apr 2015 and Sep 2019 at the Masih Daneshvari Hospital, Tehran, Iran. Allele frequencies from the genomic DNA of blood cells were studied using PCR-RFLP and their association with the risk of lung cancer was evaluated. Results The rs2910164C allele (OR = 1.56, 95% CI = 1.10–2.21, p = 0.012) and CC genotype (OR = 2.93, 95% CI = 1.07–7.9, p = 0.034, respectively) were associated with a significantly increased risk for lung cancer compared to that for the GG genotype. When patients were stratified according to smoking exposure, no association with rs2910164 variants was found. The AT genotype (OR = 0.57, 95% CI = 0.33–0.99, p = 0.048) and the A allele frequency (OR = 0.58, 95% CI = 0.35–0.98, p = 0.043) in rs767649 were lower in NSCLC patients in comparison with the control group. In addition, the rs767649 AT genotype frequency in smoking controls was higher than in smoking NSCLC patients (OR = 0.44, 95% CI = 0.21–0.90, p = 0.024). No association was found between rs2910164 and rs767649 variants and stage or type of NSCLC. Conclusion Our finding suggests that miR-146a rs2910164 and miR-155 rs767649 polymorphisms may be considered as genetic risk factors for the susceptibility to NSCLC in the Iranian population. However, a larger multicenter study across Iran is needed to confirm these findings.

Combined Effects of PVT1 and MiR-146a Single Nucleotide Polymorphism on the Lung Function of Smokers with Chronic Obstructive Pulmonary Disease.

Non-coding RNAs play an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). This study was performed to investigate the role of PVT1 and miR-146a single nucleotide polymorphisms (SNPs) in the lung function of COPD smokers. Real-time PCR and Western blot analyses were performed to measure the expression of miR-146 and PVT1 SNPs and determine the effect of these SNPs on the pathogenesis of COPD. A total of 100 COPD smokers were enrolled in this study and divided into four groups as follows: Rs2910164CC/GC + Rs13281615GG; Rs2910164CC/GC + Rs13281615GA/AA; Rs2910164GG + Rs13281615GG; and Rs2910164GG + Rs13281615GA/AA. No obvious differences in terms of age, sex, and body height and weight were found among the four groups. However, the Rs2910164GG + Rs13281615GA/AA was associated with the highest stage of the Global Initiative for Chronic Obstructive Lung Disease and the highest values of the forced vital capacity, forced expiratory volume, and diffusing capacity of carbon monoxide, while the lowest values of these parameters were observed in the Rs2910164CC/GC + Rs13281615GG group. In addition, the highest and lowest COX2 levels were observed in the Rs2910164GG + Rs13281615GA/AA and Rs2910164CC/GC + Rs13281615GG groups, respectively. PVT1 directly and negatively regulated the miR-146a expression, which in turn directly and negatively regulated COX2 expression. Thus, the combined actions of SNP in PVT1 Rs13281615 and miR-146a Rs2910164 affected the lung function in COPD smokers.

Association between miR-146a single nucleotide polymorphism and genetic susceptibility to hepatocellular carcinoma: a meta-analysis

Objective: To investigate the association between miR-146a single nucleotide polymorphism and genetic susceptibility to hepatocellular carcinoma (HCC). Methods: PubMed, Web of Science, Cochrane Library, Wanfang Data, and Google Scholar were searched for case-control studies on the association between miR-146a single nucleotide polymorphism and genetic susceptibility to HCC published up to October, 2016 in Chinese or English. The Q-statistics test was used to evaluate the heterogeneity of these articles. Results: A total of 18 articles with 5 610 cases and 7 531 controls were included for the meta-analysis. There was no significant association between miR-146a single nucleotide polymorphism and genetic susceptibility to HCC. The odds ratio (OR), 95% confidence interval (95% CI), and P values for the five genetic models were as follows: the allele model C/G (OR = 0.99, 95% CI 0.88-1.06, P = 0.440); the heterozygous model CG/GG (OR = 0.99, 95% CI 0.90-1.10, P = 0.898); the homozygous model CC/GG (OR = 0.91, 95% CI 0.75-1.10, P = 0.314); the dominant model CC+CG/GG (OR = 0.97, 95% CI 0.79-1.19, P = 0.759); the recessive model CG+GG/CC (OR = 1.05, 95% CI 0.94-1.18, P = 0.405). A subgroup analysis of race, source of control population, and Hardy-Weinberg equilibrium were performed in these five genetic models, and miR-146a single nucleotide polymorphism increased the susceptibility to HCC only in the control population-based subgroups of the recessive model CG+GG/CC (OR = 1.20, 95% CI 1.02-1.40, P = 0.024). There was no association between miR-146a rs2910164 polymorphism and susceptibility to HCC in all the other subgroups. A stratified analysis of HBV infection revealed that miR-146a rs2910164 polymorphism increased the risk of HBV-positive HCC (OR = 1.26, 95% CI 1.10-1.49, P = 0.001). Conclusion: There is no significant association between miR-146a rs2910164 polymorphism and the risk of HCC, but miR-146a rs2910164 polymorphism may increase the risk of HBV-positive HCC.

Evaluation of a Panel of Single-Nucleotide Polymorphisms in miR-146a and miR-196a2 Genomic Regions in Patients with Chronic Periodontitis.

Periodontitis is an inflammatory disease caused by bacterial triggering of the host immune-inflammatory response, which in turn is regulated by microRNAs (miRNA). Polymorphisms in the miRNA pathways affect the expression of several target genes such as tumor necrosis factor-α and interleukins, which are associated with progression of disease. The objective of this study was to identify the association between the MiR-146a single nucleotide polymorphisms (SNPs) (rs2910164, rs57095329, and rs73318382), the MiR-196a2 (rs11614913) SNP and chronic periodontitis. Genotyping was performed for the MiR-146a (rs2910164, rs57095329, and rs73318382) and the MiR-196a2 (rs11614913) polymorphisms in 180 healthy controls and 190 cases of chronic periodontitis by the direct Sanger sequencing technique. The strength of the association between the polymorphisms and chronic periodontitis was evaluated using logistic regression analysis. Haplotype and linkage analyses among the polymorphisms was performed. Multifactorial dimensionality reduction was performed to determine epistatic interaction among the polymorphisms. The MiR-196a2 polymorphism revealed a significant inverse association with chronic periodontitis. Haplotype analysis of MiR-146a and MiR-196a2 polymorphisms revealed 13 different combinations, of which 5 were found to have an inverse association with chronic periodontitis. The present study has demonstrated a significant inverse association of MiR-196a2 polymorphism with chronic periodontitis.

Micro RNA-146a But Not IRAK1 is Associated with Rheumatoid Arthritis in the Tunisian Population.

Rheumatoid arthritis (RA) is characterized by the production of an array of proinflammatory cytokines through the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway. Interleukin-1 receptor (IL-1R) and Toll-like receptors contain a common cytoplasmic motif the Toll/IL-1R (TIR) homology domain. This motif is required for NF-κB activation. IL-1R-associated kinase 1 (IRAK1) is a key adapter molecule recruited during the signaling cascade of the TIR. Its gene expression is regulated by the micro-RNA (miR)-146a. We investigated the role of IRAK1 single-nucleotide polymorphism (SNP) rs3027898 (IRAK1 rs3027898) and miR-146a SNP rs2910164 (miR-146a rs2910164) in Tunisian patients with RA and their association with C reactive protein (CRP), rheumatoid factor (RF), anticyclic citrullinated peptide (anti-CCP) antibodies, and erosion. In a cohort of 172 adult RA patients and 224 matched controls, IRAK1 rs3027898 genotyping was determined by mutagenically separated polymerase chain reaction (MS-PCR) with newly designed primers, and miR-146a rs2910164 genotyping was determined by fragment length polymorphism PCR-restriction (RFLP-PCR). The IRAK1 rs3027898 A allele was detected in 67% of RA patients and 70% of controls indicating that it is not associated with RA in codominant, dominant, or recessive models even after stratification by age and gender. The miR-146a rs2910164 G allele was detected in 76% of RA patients and 68% of controls, thus the C allele confers some protection based on a dominant model [CC+GC (odds ratio (95% confidence interval) = 0.6 (0.3-0.9), p = 0.03)]. No association with CRP, RF, anti-CCP, or erosion was found for either SNPs. The IRAK1 rs3027898 was not associated with RA, whereas C allele of miR-146a rs2910164 was found to be protective. Functional studies are required to investigate the exact role of miR-146a rs2910164 during RA.

Association between the three functional miR-146a single-nucleotide polymorphisms, rs2910164, rs57095329, and rs2431697, and autoimmune disease susceptibility: A meta-analysis

Studies suggest associations between the miR-146a single nucleotide polymorphisms (SNPs) and susceptibility to autoimmune diseases. However, the results are inconsistent and inconclusive. Therefore, the aim of this study was to arrive at a conclusion about the association between the three functional miR-146a SNPs and autoimmune disease risk. Studies were identified through PubMed/MEDLINE searches for studies published up to January 2016 using as keywords rs2910164, rs57095329, rs2431697, and miR-146a polymorphisms. Thirty studies were included in the meta-analysis. The SNP rs2910164 G > C was found to be associated with increased risk of multiple sclerosis (CC + CG versus GG, OR = 1.25, 95% CI: 1.01–1.55), with decreased risks of psoriasis (C versus G, OR = 0.81, 95% CI: 0.69–0.96; CC versus GC + GG, OR = 0.73, 95% CI: 0.56–0.94), Behcet’s disease (CC versus GC + GG, OR = 0.60, 95% CI: 0.50–0.73), asthma (C versus G, OR = 0.80, 95% CI: 0.69–0.93; CC versus GC + GG, OR = 0.65, 95% CI: 0.48–0.86), and uveitis (CC + CG versus GG, OR = 0.61, 95% CI: 0.49–0.77). The SNP rs2431697 C > T was found to be associated with an increased risk of SLE (T versus C, OR = 1.26, 95% CI: 1.15–1.38; TC + TT versus CC, OR = 1.28, 95% CI: 1.03–1.58; TT versus TC + CC, OR = 1.40, 95% CI: 1.21–1.62). The SNP rs57095329 A > G was found to be associated with an increased risk of SLE (G versus C, OR = 1.25, 95% CI: 1.17–1.35). The miR-146a SNPs rs2910164, rs57095329, rs2431697 are associated with susceptibility to certain autoimmune diseases. However, for other autoimmune diseases, they may be protective or insignificant.

Genetic variant of miR-146a rs2910164 C>G and gastric cancer susceptibility.

The single nucleotide polymorphism (SNP) rs2910164 G>C within miR-146a has been reported that is associated with the increased risk of gastric cancer (GCa). However, the results are inconclusive, espicially among Asian populations, which probably due to small sample size in each single study. To validate this association and get a more precise estimation, we conducted a large GCa study including 1,125 cases and 1,196 controls in an eastern Chinese population. Our results showed that this SNP was not associated with GCa risk in either of the three genetic models [co-dominant model: CG vs. CC, odds ratio (OR) = 0.99, 95% confidence interval (95%CI): 0.83-1.19; GG vs. CC, OR = 1.03, 95%CI: 0.81-1.32; dominant model: (CG+GG) vs. CC, OR = 1.00, 95%CI = 0.84-1.19; recessive model: GG vs. (CG+CC), OR = 1.04, 95%CI = 0.83-1.29]. Stratified analysis by age, gender, smoking status, drinking status, or tumor location confirmed this non-significant association. In summary, these results suggest that the miR-146a SNP rs2910164 may not be a risk factor for GCa in this Chinese population. Larger and well-designed, preferably prospective studies are needed to further confirm our findings.

The associations of nucleotide polymorphisms in mir-196a2, mir-146a, mir-149 with lung cancer risk.

Many studies have explored the associations between microRNAs (miRNAs) polymorphisms and lung cancer susceptibility. However, due to their limited statistical sizes, some discrepancies were discovered in these studies. This article summarized eligible studies to identify the roles of miRNAs polymorphisms in lung cancer, and analyzed the associations of polymorphisms in mir-196a2, mir-146a and mir-149 with lung cancer risk respectively. The PubMed, Web of Science, ScienceDirect and CNKI databases were searched updated to May 30, 2014. The complete data of three miRNAs polymorphisms for lung cancer were analyzed by odd ratios (ORs) and 95% confidence intervals (CIs). Finally, four studies about mir-196a2 single nucleotide polymorphism (SNP), two studies about mir-146a SNP, three studies about mir-149 SNP were investigated in this analysis. The mir-196a2 polymorphism was revealed to be associated with lung cancer susceptibility (additive model: OR=1.120, 95%CI 1.030 ∼ 1.217, P=0.008; dominant model: OR=1.118, 95%CI 1.039 ∼ 1.357, P=0.011; recessive model: OR=1.133, 95%CI 0.987 ∼ 1.300, P=0.077). However, no relationships were discovered between mir-146a or mir-149 polymorphism and lung cancer risk. This meta-analysis demonstrates that mir-196a2 SNP influences the susceptibility of lung cancer. Mir-146a and mir-149 SNP do not play a role in lung cancer risk. These findings need more validation by larger studies.

Common polymorphisms in MIR146a, MIR128a and MIR27a genes contribute to neuropathy susceptibility in type 2 diabetes

Diabetic polyneuropathy (DPN) and cardiovascular autonomic neuropathy (CAN) are common type 2 diabetes complications with a large inter-individual variability in terms of clinical manifestations and severity. Our aim was to evaluate a possible involvement of genetic polymorphisms in miRNA regions in the susceptibility to DPN and CAN. Nine polymorphisms in miRNA genes were studied in a sample of 132 type 2 diabetes patients (T2D) analysed for DPN and 128 T2D patients analysed for CAN. A genotype-phenotype correlation analysis was performed. The T allele of rs11888095 single nucleotide polymorphism (SNP) in MIR128a was significantly associated with a higher risk (ORadj=4.89, P adj=0.02), whereas the C allele of rs2910164 SNP in MIR146a was associated with a lower risk to develop DPN (ORadj=0.49, P adj=0.09), respectively. A multivariate logistic regression analysis confirmed that both SNPs contribute to DPN (p<0.001 and p=0.01 for MIR128a and MIR146a, respectively). MIR128a SNP significantly contributed also to DPN score (p=0.026). Rs895819 SNP in MIR27a was significantly associated with a higher risk to develop early CAN (P adj=0.023 and ORadj=3.43). The rs2910164 SNP in MIR146a showed a protective effect respect to early CAN (P adj=0.052, ORadj=0.32) and to confirmed CAN (P adj=0.041, ORadj=0.13). The same SNP resulted significantly associated with a lower CAN score and a higher E/I (p=0.002 and p=0.003, respectively). In conclusion, we described associations of MIR128a and MIR146a SNPs with DPN susceptibility and of MIR146a and MIR27a SNPs with CAN susceptibility. This is the first study showing that genetic variability in miRNA genes could be involved in diabetic neuropathies susceptibility.

Association Analysis of Single Nucleotide Polymorphisms in miR-146a and miR-196a2 on the Prevalence of Cancer in Elderly Japanese: A Case-Control Study

Single nucleotide polymorphisms (SNPs) affecting microRNA (miR) sequences may influence carcinogenesis. Our current study primarily aimed to confirm previously conducted association studies between rs2910164 found on miR-146a, and rs11614913 located on miR-196a2 polymorphisms and cancer phenotypes in the Japanese elderly population. rs2910164 (G/C) and rs11614913 (T/C) polymorphisms were determined by genotyping on the samples collected from 1,351 consecutive autopsy cases registered in the Japanese SNPs for geriatric research (JG-SNP) data base. Cancer samples were systematically reviewed, pathologically verified and assessed with respect to miR-146a and miR-196a2 genotypic variation. The current study covered 726 males and 625 females with a mean age of 80.3±8.9 years. The study included 524 subjects without cancer and 827 subjects with at least one type of cancer, such as gastric (n=160), lung (n=148), colorectal (n=116) or others. Males with cancers (n=467) were more numerous than females (n=360). Both rs11614913 (CT: TT adjusted odds ratio (OR) 95% confidence interval (95%CI)=0.98 (0.75-1.28), p=0.873, CC: TT adjusted OR (95%CI)=1.06 (0.76-1.47), p=0.737, CT+CC: TT, adjusted OR (95%CI)=0.99 (0.77-1.29), p=0.990), and rs2910164 (CG: CC adjusted OR (95%CI)=1.12 (0.87-1.44), p=0.383, GG: CC adjusted OR (95%CI)=1.03 (0.71-1.48), p=0.887, CG+GG: CC adjusted OR (95%CI)=1.10 (0.87-1.39), p=0.446) polymorphisms did not show significant association with overall cancer in all subjects. However, "CC" genotype in rs11614913 polymorphism was significantly associated with increased gastric cancer (n=160) in all subjects (CC: CT+TT, adjusted OR (95%CI)=1.50 (1.02-2.22), p=0.040). We found that rs11614913 and rs2910164 do not pose general cancer risk, but rs11614913 may influence gastric cancer in Japanese elderly population. Confirmation of our study results requires further investigations with larger subject populations.

Associations of Single Nucleotide Polymorphisms in miR-146a, miR-196a, miR-149 and miR-499 with Colorectal Cancer Susceptibility

MicroRNAs (miRNAs) are an abundant class of endogenous small non-coding RNAs of 20-25 nucleotides in length that function as negative gene regulators. MiRNAs play roles in most biological processes, as well as diverse human diseases including cancer. Recently, many studies investigated the association between SNPs in miR-146a rs2910164, miR-196a2 rs11614913, miR-149 rs229283, miR-499 rs3746444 and colorectal cancer (CRC), which results have been inconclusive. PubMed, EMBASE, CNKI databases were searched with the last search updated on November 5, 2013. For miR-196a2 rs11614913, a significantly decreased risk of CRC development was observed under three genetic models (dominant model: OR = 0.848, 95%CI: 0.735-0.979, P = 0.025; recessive model: OR = 0.838, 95%CI: 0.721-0.974, P = 0.021; homozygous model: OR = 0.754, 95%CI: 0.627-0.907, P = 0.003). In the subgroup analyses, miR-196a2*T variant was associated with a significantly decreased susceptibility of CRC (allele model: OR = 0.839, 95%CI: 0.749-0.940, P = 0.000; dominant model: OR = 0.770, 95%CI: 0.653-0.980, P = 0.002; recessive model: OR = 0.802, 95%CI: 0.685-0.939, P = 0.006; homozygous model: OR = 0.695, 95%CI: 0.570-0.847, P = 0.000). As for miR-149 rs2292832, the two genetic models (recessive model: OR = 1.199, 95% CI 1.028-1.398, P = 0.021; heterozygous model: OR = 1.226, 95% CI 1.039-1.447, P = 0.013) demonstrated increased susceptibility to CRC. On subgroup analysis, significantly increased susceptibility of CRC was found in the genetic models (recessive model: OR = 1.180, 95% CI 1.008-1.382, P = 0.040; heterozygous model: OR = 1.202, 95% CI 1.013-1.425, P = 0.013) in the Asian group. These findings supported that the miR-196a2 rs11614913 and miR-149 rs2292832 polymorphisms may contribute to susceptibility to CRC.

The Associations of Single Nucleotide Polymorphisms in miR-146a, miR-196a and miR-499 with Breast Cancer Susceptibility

BackgroundPrevious studies have investigated the association between single nucleotide polymorphisms (SNPs) located in microRNAs (miRNAs) and breast cancer susceptibility; however, because of their limited statistical power, many discrepancies are revealed in these studies. The meta-analysis presented here aimed to identify and characterize the roles of miRNA SNPs in breast cancer risk, and evaluate the associations of polymorphisms in miR-146a rs2910164, miR-196a rs11614913 and miR-499 rs3746444 with breast cancer susceptibility, respectively.Methodology/Principal FindingsThe PubMed and Embases databases were searched updated to 31st December, 2012. The complete data of polymorphisms in miR-146a rs2910164, miR-196a rs11614913 and miR-499 rs3746444 from case-control studies for breast cancer were analyzed by odds ratios (ORs) with 95% confidence intervals (CIs) to reveal the associations of SNPs in miRNAs with breast cancer susceptibility. Totally, six studies for rs2910164 in miR-146a, involving 4225 cases and 4469 controls; eight studies for rs11614913 in miR-196a, involving 4110 cases and 5100 controls; and three studies of rs3746444 in miR-499, involving 2588 cases and 3260 controls, were investigated in the meta-analysis. The rs11614913 (TT+CT) genotype of miR-196a2 was revealed to be associated with a decreased breast cancer susceptibility compared with the CC genotypes (OR = 0.906, 95% CI: 0.825–0.995, P = 0.039); however, no significant associations were observed between rs2910164 in miR-146a (or rs3746444 in miR-499) and breast cancer susceptibility.ConclusionsThis meta-analysis demonstrates the compelling evidence that the rs11614913 CC genotype in miR-196a2 increases breast cancer risk, which provides useful information for the early diagnosis and prevention of breast cancer.

Association Between Two Genetic Variants in miRNA and Primary Liver Cancer Risk in the Chinese Population

MicroRNAs (miRNAs) play an important role in the growth and development of human beings. Single nucleotide polymorphisms (SNPs) within miRNA could change their production or affinity with target genes, thus leading to malignant diseases. This case-control study conducted in Western China aimed to explore the relationship between polymorphisms in miR-146a (rs2910164 G>C) and miR-499 (rs3746444 T>C) and primary liver cancers in the Chinese population. 186 primary liver cancer cases and 483 healthy controls were genotyped using polymerase chain reaction-restriction fragment length polymorphism. No significant differences were observed between distributions of the two SNPs and susceptibility of primary liver cancer or diverse clinicopathologic features. However, we found that patients with genotype CG of the SNP in miR-146a tended to have earlier onset and better liver function than patients with genotype CC (average age: 49.9 vs. 54.9, p=0.038; average Child-Pugh grade: 5.55 vs. 6.15, p=0.021), and further analysis showed that patients who had at least one G allele were diagnosed at an earlier age (average age: 49.6 vs. 54.9, p=0.022) and had better liver function (average Child-Pugh grade:5.60 vs. 6.15, p=0.026). Our data suggested lack of association between the two SNPs and primary liver cancer risk, though, interestingly, the miR-146a SNP may influence the age of onset and Child-Pugh grade.