Associations of Single Nucleotide Polymorphism in miR-146a Gene with Susceptibility to Breast Cancer in the Iranian Female.
ABSTRACT: BACKGROUND:MicroRNAs (miRNAs), short regulatory RNAs, function as negative regulators able to modulate gene expression. Just as other genetic variant, single nucleotide polymorphisms (SNPs) in miRNA genes, may have an impact on their expression and/or maturation and hence leading to different consequences in carcinogenesis. Accordingly, this study aimed to assess the frequency of miR-146a G/C (rs2910164) polymorphism and its association with susceptibility to breast cancer in Iranian women. METHODS:We conducted a case-control study using Tetra ARMS polymerase chain reaction (Tetra ARMS PCR) method in 100 Iranian female participants (50 breast cancer patients and 50 controls). Besides, a number of sequenced samples were chosen to confirm the accuracy of genotyping by Tetra ARMA PCR. SPSS software was utilized for all statistical analyses. The odds ratios (ORs) and 95% confidence intervals (95% CIs) were applied to analyze the association between the SNP frequency and breast cancer. RESULTS:The frequency of genotypes for G/G, G/C, and C/C were 23 (46%), 26 (52%), and 1 (2%) among cases and 15 (30%), 33 (66%), and 2(4%) among controls, respectively. The results generated by the groups did not show any significant correlation between miR-146a G/C (rs2910164) polymorphism and breast cancer, either at genotype or allele levels (P>0.05). F-SNP-based in silico analysis indicated possible modifications in transcriptional regulations induced by miR-146a G/C (rs2910164) variations. CONCLUSION:Overall, our results indicated no correlation between miR-146a G/C (rs2910164) polymorphism and genetic susceptibility to breast cancer in Iranian female populations. However, these findings need to be further confirmed by analyses of a larger number of cases.
Project description:MicroRNAs (miRNAs) play an important role in regulating gene expression at the post-transcriptional level and are involved in numerous physiological processes. Accumulating evidence suggests that single-nucleotide polymorphisms (SNPs) in human miRNA genes may affect miRNA biogenesis pathway and influence the susceptibility to several diseases such as cancer. The present study aimed to evaluate the impact of miR-499 rs3746444, miR-196a2 rs11614913, miR-149 rs2292832, and miR-146a rs2910164 polymorphisms on prostate cancer (PCa) risk in a sample of Iranian population. This case-control study was done on 169 patients with pathologically confirmed PCa and 182 benign prostatic hyperplasia (BPH). The genotyping assays were done using T-ARMS-PCR or PCR-RFLP methods. The findings indicated that CC genotype of miR-499 rs3746444 polymorphism increased the risk of PCa (OR = 1.76, 95% CI = 1.12-2.79, P = 0.019) compared to TT genotype. No statistically significant association was found between miR-196a2 rs11614913, miR-149 rs2292832, and miR-146a rs2910164 polymorphisms and PCa risk. In summary, the findings indicated that miR-499 rs3746444 polymorphism increased the risk of PCa in an Iranian population. Further studies with larger sample sizes and different ethnicities are necessary to verify the findings of the present study.
Project description:Single-nucleotide polymorphisms (SNPs) in miRNAsmay alter its expression levels or processing and contribute to susceptibility to a wide range of diseases. Our study aimed to evaluate the possible association between miRNA-146a rs2910164 and miRNA-499 rs3746444 polymorphisms and susceptibility to pulmonary tuberculosis (PTB) in a sample of Iranian population. This case- control study was performed on 202 PTB patients and 204 healthy individuals. Genotyping was performed using tetra amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR). The results indicated that neither miRNA-499 rs3746444 nor miRNA-146a rs2910164 are associated with the risk of PTB in a sample of Iranian population. Larger studies with different ethnicities are required to validate our findings.
Project description:This study provides evidence that the common rs2910164 polymorphism in miR-146a strongly correlates with lung cancer risk in nonsmoking females in northeast China. The genotypes of miR-146a rs2910164 were determined in 1131 patients with lung cancer and 1003 healthy control subjects. Tissue samples were used to evaluate the association between miRNA expression and lung cancer risk as well as the correlation between rs2910164 genotypes and miR-146a expression. The secondary structures of the wild-type and variant miR-146a sequences were predicted, and luciferase-based target assays were used to test whether miR-146a bound to tumor necrosis factor receptor associated factor 6 (TRAF6) mRNA. Individuals carrying heterozygous CG genotype of miR-146a rs2910164 had less risk of lung cancer than those carrying homozygous wild CC genotype (OR = 0.76, 95% CI = 0.60-0.98, P = 0.032). We found no significant association between miR-146a expression and lung cancer risk. MiR-146a expression differed in those carrying the CC genotype as compared with the CG or the GG genotype (P = 0.032 and 0.001), and the secondary structure of the C allele differed slightly from the G allele. Significantly lower levels of luciferase activity were observed when the TRAF6 3'UTR was cotransfected with miR-146a-3p carrying the rs2910164 C allele (P = 0.001). Thus, miR-146a rs2910164 polymorphism may influence susceptibility to lung cancer in Chinese nonsmoking females through targeting TRAF6.
Project description:OBJECTIVE: MicroRNAs (miRNAs) are short regulatory RNAs that can modulate gene expression and function as negative regulators. Common genetic variants like single nucleotide polymorphisms (SNPs) in miRNA genes may alter their expression or maturation resulting in varied functional consequences in carcinogenesis. Therefore, we evaluated the genetic variants in pre-miRNAs: hsa-miR-146a G/C (rs2910164), hsa-miR-196a2 C/T (rs11614913), and hsa-miR-499 T>C (rs3746444) for their role in breast cancer susceptibility. STUDY DESIGN: The study comprised 121 breast cancer patients, 115 with benign breast disease, and 164 controls. The genotypic frequency of miRNA polymorphisms was determined by PCR-RFLP assay. Logistic regression was used for statistical analysis using SPSS Software version 15.0. In silico analysis was done using various bioinformatics tools (F-SNP, FAST-SNP). RESULTS: The heterozygous variant of miR-146a G/C (rs2910164) is associated with the reduced risk of breast cancer at the genotype level as well as at the allele level (p < 0.05, OR = 0.5) as compared to controls. On the contrary, no significant difference was observed in the distribution of miR-196a2 C/T (rs11614913) and miR-499 T>C (rs3746444) polymorphisms in any groups both at genotype and allele levels. On the other hand, in multivariate analysis, we found that the miR-196a2 (rs11614913) C>T was associated with an increased risk of breast cancer risk in postmenopausal females (p = 0.02, OR = 3.2). We also attempted to find out the risk of malignant breast disease in relation to each of the above SNPs on dividing our data on the basis of benign and malignant status, but no significant difference was observed. In silico analysis using F-SNP showed change in transcriptional regulation by miR-146a G/C (rs2910164), miR-196a2 C/T (rs11614913) and miR-499 T>C (rs3746444) variations; the functional score was 0.100, 0.065 and 0.277, respectively. CONCLUSION: The results of the present study demonstrate that miR-146a G/C (rs2910164) polymorphism is associated with reduced genetic susceptibility to breast cancer. However, multivariate analysis showed as miR-196a2 (rs11614913) C>T to be associated with increased risk of breast cancer risk in postmenopausal females. Further multicentric studies involving a large number of cases need to be carried out to strengthen the present results.
Project description:BACKGROUND: Evidence has shown that single nucleotide polymorphism located in pre-miRNA or mature microRNA may modify various biological processes and affect the processing of carcinogenesis. Published results about the association between miR-146a rs2910164 G/C polymorphism and human gastric cancer susceptibility are inconclusive. The aim of this study was to acquire a more precise effect of the association between the miR-146a rs2910164 polymorphism and gastric risk by meta-analysis. METHODS: Eligible genetic association studies were searched from PubMed, Web of Knowledge and Chinese Biomedicine Database on human subject. Quantitative data synthesis was conducted for the associations of miR-146a rs2910164 G/C polymorphism with susceptibility to gastric cancer. RESULTS: Nine eligible studies that included a total of 3,885 gastric cancer patients and 5,396 controls were identified in the present meta-analysis. The overall OR indicated a potential association between rs2910164 polymorphism and GC but the effect was not statistically significant (GG vs. CG/CC: OR = 1.076, 95% CI 0.925-1.251, P = 0.342). When stratifying for population, the result showed that miR-146a rs2910164 GG genotype was associated with increased gastric cancer risk among Chinese in recessive model (GG vs. CG/CC: OR = 1.171, 95% CI 1.050-1.306, P = 0.005). Besides, no significant difference was found in gender, smoking, location, metastasis of lymph node and Laurèn's classification. CONCLUSIONS: The present meta-analysis suggests an increased risk between miR-146a rs2910164 GG genotype and gastric cancer susceptibility in Chinese based on published literatures.
Project description:BACKGROUND: Previous 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 FINDINGS: The PubMed and Embases databases were searched updated to 31(st) 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. CONCLUSIONS: This 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.
Project description:AIM:To analyse the relationship between two potentially functional single-nucleotide polymorphisms (SNPs) of the miR-146a gene (rs2910164 and rs57095329) and the risk of atherosclerotic cerebral infarction (ACI). METHODS:A total of 297 patients with ACI and 300 matched healthy individuals were enrolled in the study. The miR-146a polymorphism was detected using the polymerase chain reaction-restriction fragment length polymorphism method. RESULTS:A significant difference in the C allele frequency at rs2910164 (p=0.028) was noted between patients with ACI and control subjects. In contrast, the genotype and allele frequencies of rs57095329 were not statistically associated with ACI. In addition, the decreased expression of miR-146a was significantly more frequent in ACI patients who were ApoE?4 (?) carriers (p=0.0233), and rs2910164 G?C was intimately associated with the ApoE?4-containing genotype in patients compared with the ApoE?4 (?) carriers (p=0.0323). CONCLUSIONS:Our findings indicated that the C allele of rs2910164 miR-146a is an important risk factor for ACI, and ApoE?4 may function through attenuating miR-146a expression to enhance ACI susceptibility. This study provides new information about the possible relationship between miR-146a and ApoE?4 in the development of ACI, with potentially important therapeutic implications.
Project description:To systematically evaluate the association between the miR-146a rs2910164 polymorphism and susceptibility to gastric cancer.A comprehensive electronic search was conducted for articles published up until January 27, 2014 in Medline (PubMed), Excerpta Medica Database (Embase), the Cochrane Library and Google Scholar. Only case-control studies published in English that evaluated the association between the miR-146a rs2910164 polymorphism and susceptibility to gastric cancer were included. Furthermore, only studies with sufficient data allowing for calculation of odds ratio (OR) and corresponding 95% confidence interval (CI) were included. These values were used in the quantitative synthesis to assess the strength of the association between the miR-146a rs2910164 polymorphism and risk of gastric cancer.The database search identified 1002 eligible studies, of which seven (comprising 4112 cases and 5811 controls) were included for the meta-analysis. The results indicate that miR-146a rs2910164 polymorphism is more likely to be associated with gastric cancer risk. In the overall analysis, a significantly increased cancer risk was found in the heterozygote (GG vs GC) comparison (OR = 1.14, 95%CI: 1.03-1.27; P = 0.01 for pooled OR). In the ethnicity subgroup analysis, a similar result was found among Caucasians (OR = 1.36, 95%CI: 1.01-1.85; P = 0.04 for pooled OR). In the stratified analysis by quality of studies, a significantly increased cancer risk was found in the heterozygote comparison among high quality studies (OR = 1.12, 95%CI: 1.01-1.26; P = 0.04 for pooled OR). When stratified on the basis of sample size, a significantly increased cancer risk was found among small sample size subgroups for the allelic (G vs C: OR = 1.16, 95%CI: 1.03-1.30; P = 0.01), homozygote (GG vs CC: OR = 1.33, 95%CI: 1.03-1.73; P = 0.03) and recessive model (GG vs GC + CC: OR = 0.05, 95%CI: 0.00-0.10; P = 0.03) comparisons.The miR-146a rs2910164 polymorphism is associated with increased gastric cancer risk, particularly evident in high quality studies with small sample sized Caucasian populations.
Project description:MicroRNAs (miRNAs) are small non-coding RNA molecules that function as tumor suppressors or oncogenes. Single nucleotide polymorphisms (SNPs) located in the miRNAs influence the function of mature miRNAs and may contribute to cancer development. Studies investigating the association between miR-146a rs2910164 and miR-196a2 rs11614913 polymorphisms and hepatocellular carcinoma (HCC) risk reported inconsistent results. We performed a meta-analysis of all available studies to summarize this situation. Eligible studies were identified by search of electronic databases including PubMed, Embase, and Cochrane library for the period up to August 2014. The association of miR-146a rs2910164 and miR-196a2 rs11614913 polymorphisms and HCC risk was assessed by odds ratios (ORs) together with their 95% confidence intervals (CIs). Finally, a total of 12 studies with 4171 cases and 4901 controls were included for miR-146a rs2910164 polymorphism and 10 studies with 4687 cases and 4990 controls were available for miR-196a2 rs11614913 polymorphism. With respect to miR-146a rs2910164 polymorphism, statistical significant increased HCC risk was found when all studies were pooled into the meta-analysis (GG+CG vs CC: OR = 1.097, 95% CI 1.005-1.197, P = 0.037). In subgroup analyses by ethnicity, source of control, and HWE in controls, significant increase of HCC risk was found in Asians, population-based studies, and studies consistent with HWE, but not in Caucasians, hospital-based studies, and studies inconsistent with HWE. With respect to miR-196a2 rs11614913 polymorphism, no significant association with HCC risk was found in the overall and subgroup analyses. The results suggest that the miR-146a rs2910164 polymorphism contributes to increased HCC susceptibility, especially in Asian populations. Further large and well-designed studies are required to validate this association.
Project description:miR-146a plays a critical role in innate immune and inflammatory responses. Kawasaki disease involves immune-mediated inflammatory responses, which leads to vascular endothelial injury. However, there has been no study on the association between the miR-146a rs2910164 C>G polymorphism and Kawasaki disease risk. We enrolled 532 Kawasaki disease patients and 623 healthy controls from southern Chinese population, and the miR-146a rs2910164 C>G polymorphism was genotyped by the TaqMan method. There was no evidence that this polymorphism was associated with Kawasaki disease. Stratified analysis also showed no significant association. The present study indicates that the miR-146a rs2910164 C>G polymorphism may not be associated with Kawasaki disease in the southern Chinese population. Larger multicenter studies are needed to confirm our conclusions.