miR-146a Rs2910164 Polymorphism Research Articles

MicroRNA variants in endometriosis and its severity

ABSTRACT Background: MicroRNAs (miRNAs) are naturally occurring posttranscriptional regulatory molecules that potentially play a role in endometriotic lesion development. Method: We evaluated the prevalence of miRNAs variants miR-146a rs2910164, miR-149 rs2292832, miR-196a2 rs11614913, and miR-499 rs3746444 in endometriosis in 260 cases and 260 controls. DNA was extracted and genotyping of the SNPs was carried out by PCR. Results: There was a significant association of rs2910164 and rs2292832 with increased rates of endometriosis under the dominant (p < 0.001), recessive (p < 0.05), co-dominant (p < 0.001), and allelic model (p < 0.001). Also, rs3746444 showed a borderline association with endometriosis under the recessive model (p = 0.05); however, rs11614913 was not linked to endometriosis. Further analysis indicated the significant association of miR-146a rs2910164 polymorphism genotypes (GG, GC, and CC) and miR-149 rs2292832 genotypes (CC and CT) with endometriosis severity in patients (p < 0.001). Additionally, haplotype frequency in cases compared to controls and Linkage disequilibrium (LD) between the mentioned SNPs was appraised. Conclusion: MiR-146a, miR-149 and miR-499 may have a role in the pathogenesis of endometriosis.

Association between miR-27a rs895819 polymorphism and breast cancer susceptibility: Evidence based on 6118 cases and 7042 controls.

Background:Polymorphism in miR-27a rs895819 has been associated with breast cancer (BC) risk, but studies have reported inconsistent results. This meta-analysis investigated the possible association between miR-27a rs895819 polymorphism and BC risk.Methods:PubMed, EMBASE, Google Scholar, and the Chinese National Knowledge Infrastructure (CNKI) databases were systematically searched to identify relevant studies in English and Chinese. Meta-analyses were performed to examine the association between miR-27a rs895819 and BC susceptibility.Results:A total of 16 case–control studies involving 6118 cases and 7042 controls were included. Analysis using five genetic models suggested no significant association between miR-27a rs895819 polymorphism and BC risk in the total population, or specifically in Asian or Chinese subpopulations. In the Caucasian subpopulation, however, the G-allele and AG genotype at rs895819 were significantly associated with decreased BC risk according to the allelic model (OR 0.90, 95% CI 0.84–0.97, P = .004) and heterozygous model (OR 0.89, 95% CI 0.81–089, P = .02), while the wild-type AA genotype was significantly associated with increased BC risk according to the dominant model (OR 1.13, 95% CI 1.03–1.24, P = .007).Conclusion:These results indicate that among Caucasians, the wild-type AA genotype at rs895819 may confer increased susceptibility to BC, while the G-allele and AG genotype may be protective factors. These conclusions should be verified in large, well-designed studies.

Lack of association between miR-146a rs2910164 C/G locus and colorectal cancer: from a case-control study to a meta-analysis.

Previous studies suggested that miR-146a rs2910164 (C/G) locus was predicted to influence the risk of cancer. However, the relationship of miR-146a rs2910164 locus with colorectal cancer (CRC) susceptibility was controversial. We recruited 1003 CRC patients and 1303 controls, and performed a case–control study to clarify the correlation of miR-146a rs2910164 locus with CRC risk. Subsequently, a comprehensive meta-analysis was conducted to verify our findings. In the case–control study, we suggested that miR-146a rs2910164 variants did not alter CRC risk (CG vs. CC: adjusted P=0.465; GG vs. CC: adjusted P=0.436, CG/GG vs. CC: adjusted P=0.387 and GG vs. CC/CG: adjusted P=0.589), even in subgroup analysis. Next, we conducted a pooled-analysis to identify the correlation of miR-146a rs2910164 locus with CRC risk. In this pooled-analysis, 7947 CRC cases and 12,168 controls were included. We found that miR-146a rs2910164 polymorphism did not influence the risk of CRC (G vs. C: P=0.537; GG vs. CC: P=0.517, CG/GG vs. CC: P=0.520 and GG vs. CC/CG: P=0.167). Our findings suggest that miR-146a rs2910164 C/G polymorphism is not correlated with the susceptibility of CRC. In the future, more case–control studies are needed to confirm our results.

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.

The rate of miR-146a rs2910164 mutations in patients with lung cancer: a meta-analytic review.

BackgroundWorldwide, lung cancer has become the most common cancer type and lung cancer gradually becomes the leading cause of cancer death. MiR-146a rs2910164 polymorphism might be associated with the susceptibility to lung cancer. This article will discuss the rate of miR-146 rs2910164 mutation in lung cancer and normal people.MethodsWe searched the relevant published literature from January 1, 2009, to December 31, 2019, in English or Chinese, using the PubMed, Medline, Embase, China Biology Medicine disc, China National Knowledge Infrastructure, and WanFang databases. Two reviewers extracted data from eligible studies in duplicate with a standard data collection form and reached a consensus on each item. All analyses were performed using the Review Manager.ResultsIn conclusion, the frequency of miR-146a GC genotype mutation in normal people and patients with lung cancer is 44% and 47% respectively and the rate of miR-146a CC genotype mutation in the normal people and patients with lung cancer is 17% and 22% respectively. What’s more, the frequency of miR-146a C allele mutation in normal people and patients with lung cancer is 40% and 46% respectively.ConclusionsIn conclusion, we can find that the mutation rate of the lung cancer group is higher than the normal people. In the lung cancer group, we can find that the rate of mutation is highest in Italians and lowest in Indians, both in genotypes and in allele C, in which there are significant differences. Chinese and Koreans have similar mutation rates.

404MO Clinical relevance of MIR27A rs895819 polymorphism and its interaction with DPYD variants for predicting grade 4-5 fluoropyrimidine (FP) toxicity (tox) in the FUSAFE individual patient data meta-analysis (IPD-MA)

404MO Clinical relevance of MIR27A rs895819 polymorphism and its interaction with DPYD variants for predicting grade 4-5 fluoropyrimidine (FP) toxicity (tox) in the FUSAFE individual patient data meta-analysis (IPD-MA)

The association of miR-27a rs895819 polymorphism with colorectal cancer risk in Chinese population.

BackgroundBesides environment and living habits, such as a sedentary lifestyle, smoking and drinking, genetic variation also plays an important role in the development of colorectal cancer (CRC). This study was aimed to investigate the role of miR‑27a rs895819 polymorphism on CRC risk in Chinese population.MethodsIn a case‐control study including 208 CRC and 312 age‐ and gender‐matched healthy control subjects, the rs895819 polymorphism was genotyped using the TaqMan allelic discrimination assay. Furthermore, a pooled analysis based on eligible studies was performed by using the STATA software.ResultsLogistic regression analysis showed that the rs895819 polymorphism was not associated with CRC risk. However, a pooled analysis based on five studies from Chinese population showed a statistically significant association between the rs895819 polymorphism and CRC risk (GG vs AA: OR = 1.56, 95% CI = 1.27‐1.92, Pz < .01; (AG + GG) vs AA: OR = 1.14, 95% CI = 1.01‐1.30, Pz = .04; GG vs (AG + AA): OR = 1.54, 95% CI = 1.27‐1.88, Pz < .01; G vs A: OR = 1.20, 95% CI = 1.09‐1.33, Pz < .01).ConclusionOur study suggests that miR‑27a rs895819 polymorphism plays an important role in CRC risk in Chinese population and may serve as a valuable biomarker for predicting an individual's susceptibility to CRC.

Association of miR-27a polymorphism with the risk of digestive system cancers

BackgroundCancer of the digestive system is a common cancer and results in high mortality rates world-wide. miR-27a polymorphism has been associated with an increased risk of digestive system cancers; however, this has not been conclusively shown yet. Therefore, to clarify this, we conducted a comprehensive meta-analysis. MethodsPubMed, EMBASE, OVID and Cochrane Library databases were comprehensively searched to retrieve eligible studies published up to May 10, 2020 that referred to digestive cancers. Odds ratios and the corresponding 95 % confidence intervals (CI) were used when calculating the relationship between miR-27a rs895819 polymorphism and susceptibility to digestive cancers. ResultsA significant correlation between the miR-27a rs895819 polymorphism and the presence of digestive system cancers was found in four genetic models, which were the homozygote, dominant, recessive, and allele genetic models (GG vs AA: OR = 1.210, 95 %CI = 1.020–1.436, P = 0.029; GG + AG vs AA: OR = 1.092, 95 %CI = 1.024–1.164, P = 0.007; GG vs AG + AA: OR = 1.182, 95 %CI = 1.005–1.390, P = 0.044; G vs A: OR = 1.099, 95 %CI = 1.046–1.154, P < 0.001). Hierarchical analysis by ethnicity suggested that miR-27a rs895819 significantly increased the risk of digestive system cancers in the Asian population, but not in Caucasians. Additionally, rs895819 polymorphism was found to be significantly associated with colorectal cancer and gastric cancer. ConclusionsThe miR-27a rs895819 polymorphism may be associated with an increased risk for digestive system cancers.

Association between miRNA-146a polymorphism and lung cancer susceptibility: A meta-analysis involving 6506 cases and 6576 controls.

We sought to analyze the association between miR-146a rs2910164 G > C polymorphism and susceptibility to lung cancer using a meta-analysis of case-control studies. We systematically searched for studies reporting on the relationship between miR-146a rs2910164 polymorphism and the risk of lung cancer in PubMed, Embase, Web of Science and Chinese National Knowledge Infrastructure databases. We then calculated pooled odds ratios (ORs), at 95% confidence interval (CI) to assess the aforementioned relationship. All the data were analyzed using statistical packages implemented in R version 3.6.2 (R Project for Statistical Computing), run in RStudio version 1.2.5033. A total of fifteen studies, comprising 6506 cases and 6576 controls, were enrolled in this meta-analysis. Significant associations were observed between miR-146a rs2910164 polymorphism and the risk of lung cancer based on overall pooled subjects under the allele, heterozygous, homozygous, dominant, and recessive genetic models (C vs. G: OR = 1.27, 95% CI: 1.12-1.44; GC vs. GG: OR = 1.23, 95% CI: 1.03-1.46; CC vs. GG: OR = 1.51, 95% CI: 1.18-1.93; GC + CC vs. GG: OR = 1.33, 95% CI: 1.10-1.61; CC vs. GG + GC: OR = 1.32, 95% CI: 1.13-1.53). Ethnicity-based subgroup analyses revealed no statistically significant differences in Asians using heterozygous and dominant genetic models. miR-146a rs2910164 G > C polymorphism may be a risk factor of lung cancer. Asian populations exhibiting heterozygous and dominant genotypes need to be further investigated to validate our findings.

Investigation of the Association between a Genetic Variant in MiR-196a-2 Gene and the Risk of Lung Cancer in the Iranian Population

Introduction: MicroRNAs (miRNAs) play an important role in the expression of their target genes. The single-nucleotide polymorphisms (SNPs) in miRNAs may affect their function and expression. The aim of the present study was to investigate the association between miR-196a2 rs116614913 polymorphism and non-small cell lung cancer (NSCLC) in the Iranian population.Materials and Methods: This case-control study was performed among 103 lung cancer patients and 100 healthy controls. The polymerase chain-reaction restriction fragment length polymorphism (PCR-RFLP) method and direct sequencing were used for miR-196a2 polymorphism genotyping. Statistical analyses were performed using SPSS software and t test method.Results: According to the findings of this study, there was no significant association between rs11614913 polymorphisms and the risk of lung cancer in codominant model (CT vs. CC: OR = 0.67, TT vs. CC: OR = 0.74, CT + CC vs. CC: OR = 1.133), dominant model (CT+TT vs. CC: OR=0.657) and recessive model (TT vs. CC+CT: OR = 0.88). In addition, there was no relationship between the clinicopathological characteristics of patients and controls.Conclusions: In summary, findings indicated no significant association between miR-196a2 rs11614913 polymorphisms and lung cancer in the Iranian population. Further studies with larger sample sizes are recommended to verify these findings.

Association between miR-196a2 polymorphism and the development of hepatocellular carcinoma in the Egyptian population

BackgroundHepatocellular carcinoma (HCC) is one of the most prevalent cancers worldwide. Circulating microRNAs (miRNAs) are endogenous, small (17–25 nucleotides) non-coding RNAs that are overexpressed in many human cancers including HCC. Single-nucleotide polymorphisms (SNPs) of miRNAs play an important role in the pathogenesis of HCC. In our study, we aimed to evaluate the role of miR-196a2 rs11614913 polymorphism in the development of HCC. A total of 200 subjects, including 80 HCC patients, 60 patients with liver cirrhosis, and 60 healthy controls were selected. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was taken to determine miR-196a2 rs11614913 polymorphism.ResultsThe genotype distribution of the TC and CC, TC + CC genotypes, and the C allele were significantly higher in HCC patients than control and cirrhotic groups (P = 0.02, P = 0.005, and P = 0.003, respectively). Compared with the wild-type TT genotype, both the variant TC, CC, TC + CC genotypes were associated with an elevated risk of HCC (OR = 2.77, 95% CI = 1.27–6.04), (OR = 4.94, 95% CI = 1.74–14.07), (OR = 3.24, 95% CI = 1.55–6.78) respectively. Moreover, the C allele was correlated with an increased risk of HCC (OR = 2.30, 95% CI = 1.40–3.76) compared to the wide-type T allele. Also, there is no significant correlation between the different miR-196a2 genotypes and either the clinico-pathologic features of HCC or its aggressiveness.ConclusionOur results suggest that the miR-196a2 rs11614913 polymorphism is associated with an increased risk of HCC in the Egyptian population.

Fas and microRNAs Variations as a Possible Risk for Behçet Disease.

Behçet disease (BD) belongs to a disease family that has a transparent borderline between autoinflammatory and autoimmune disorders. Fas and some miRNAs have revealed to display remarkable roles in both autoimmune and autoinflammatory processes, and they can play important roles in defective apoptosis in BD. We investigated the association of the susceptibility of BD with Fas, miRNA variations, and their both single and combined presence in a Turkish population as a case-control study. The distributions of FAS-670 A>G rs1800682, mir146a rs2910164, and mir196a rs11614913 polymorphisms are analyzed with the polymerase chain reaction-restriction fragment length polymorphism method in 115 BD patients and 220 controls in 6-month period. Statistical analysis indicates that in the case of Fas-670 A/G rs1800682, AA genotype and A allele have a protective role in BD (p = 0.0004 and p = 0.0009, respectively). The dominant model (AA + AG/GG) also displays a protective effect on BD unlike the recessive model (p = 0.03). In addition, both homozygous genotype (CC) of rs2910164 of mir-146a (p = 0.04) and the dominant model (CC + CG vs. GG) have protective effects on BD unlike the recessive model (p < 0.0001). Both mir-196a2 rs1800682 polymorphism and combined genotype analysis of rs1800682-rs2910164 and rs1800682-rs11614913 gave no statistically significant differences within the groups for genotypes and either of the alleles (p > 0.05). These findings indicate that both Fas rs1800682 and mir-146a rs2910164 variants might be important factors participating in the protection against BD in the Turkish population.

Significant Association Between the MiR146a Genotypes and Susceptibility to Childhood Acute Lymphoblastic Leukemia in Taiwan.

Mounting evidence has shown that miRNAs play a critical role in the regulation of hematopoiesis of cell proliferation and apoptosis as well as in tumorigenesis. The miR146a rs2910164 polymorphism, which is closely responsive for its expression, has been reported to associate with the risk of several solid cancers. The study aimed at examining the association of the it with susceptibility to childhood acute lymphoblastic leukemia (ALL) in Taiwan. We recruited 266 patients with childhood ALL and 266 healthy controls, and rs2910164 genotypes were determined by the polymerase chain reaction-restriction fragment length polymorphism methodology. The allele G was associated with decreased childhood ALL risk (OR=0.66, 95%CI=0.52-0.85, p=0.0011). Consistently, the GG genotype was associated with a decreased susceptibility (OR=0.40, 95%CI=0.23-0.67, p=0.0004). Patients with CG and GG genotypes were of earlier onset than those with CC genotype (p=0.0255 and p=0.0001). MiR146a rs2910164 G allele serves as a protective marker for childhood ALL in Taiwan.

Association between polymorphisms in microRNAs and susceptibility to diabetes mellitus: A meta-analysis.

Background:Accumulated evidence has indicated the associations between single-nucleotide polymorphisms (SNPs) in microRNAs (miRNAs) and the susceptibility to diabetes mellitus (DM), but the conclusions remain controversial. This study was to investigate the true contribution of miRNA SNPs to the risk of DM by using a meta-analysis of all the published studies.Methods:Relevant studies were identified in the databases of PubMed and the Cochrane Library databases. The strength of associations between miRNA polymorphisms and DM risk was assessed by odds ratios (ORs) and 95% confidence intervals (95% CIs) under five genetic models using the STATA software.Results:Six studies, containing 2773 cases and 2632 controls, were enrolled, 5 of which evaluated miR-146a (rs2910164), 4 for miR-27a (rs895819), and 3 for miR-124 (rs531564) and 2 for miR-375 (rs6715345), miR-128a (rs11888095), miR-194a (rs3820455). The meta-analysis indicated that the G allele or GG genotype of miR-146a rs2910164 was associated with a significantly increased risk for DM compared with C allele or GC/CC genotype in Latin American population; CC genotype of miR-27a rs895819 polymorphism was associated with a significantly decreased risk for DM in Asian population compared with the TT genotype; patients carrying with CC genotype of miR-124 rs531564 had a lower probability to develop DM regardless of ethnicity; no associations were identified between polymorphisms in miR-375, miR-128a, miR-194a and the susceptibility to DM.Conclusion:Our study suggests that miR-146a/miR-27a and miR-124 polymorphisms may be ethnicity-dependent or -independent susceptibility factors to DM, respectively.

Associations between miR-146a rs2910164 polymorphisms and risk of ischemic cardio-cerebrovascular diseases.

Background:Many studies investigated the association between miR-146a rs2910164 polymorphisms and risk of ischemic cardio-cerebrovascular diseases. However, the results were inconsistent.Methods:We searched the PubMed, EMBASE, Cochrane library, Web of Science, Chinese National Knowledge Infrastructure, VIP, and Wanfang databases for appropriate studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the associations. Heterogeneity, sensitivity, and publication bias were conducted to measure the robustness of our findings.All analyses were based on previous published studies, thus, no ethical approval and patient consent are required.Results:We conducted a meta-analysis to evaluate the relationship between miR-146a rs2910164 polymorphisms and risk of ischemic cardio-cerebrovascular diseases. A total of 26 related studies involving 11,602 cases and 14,016 controls were identified and included in our meta-analysis. After considering the heterogeneity of the global analysis, we inferred that rs2910164 polymorphisms were associated with a lower risk of coronary heart disease (CHD) significantly in all genetic models. In addition, it was also found that the miR-146a rs2910164 polymorphisms were associated with the low risk of ischemic cardio-cerebrovascular diseases in large sample size subgroup analysis.Conclusion:These results indicate that miR-146a rs2910164 polymorphisms were significantly associated with a lower risk of ischemic cardio-cerebrovascular. The miR-146a rs29101164 might be recommended as a predictor for susceptibility of ischemic cardio-cerebrovascular diseases.

Micro-RNA 196a2 expression and miR-196a2 (rs11614913) polymorphism in T1DM: a pilot study.

Background Recent emerging evidence supports the role of miR-196a2 in various human diseases. However, its role in type 1 diabetes mellitus (T1DM) is still underestimated. We aimed, for the first time, to investigate the expression of miR-196a2 in T1DM and the association of miR-196a2 (rs11614913) polymorphism with susceptibility of T1DM in a sample of patients from Cairo, Egypt. Methods The study included 150 patients and 150 healthy subjects. Evaluation of rs11614913 genotypes and miR-196a2 expression was done using the allelic discrimination and quantitative reverse transcriptase polymerase chain reaction (PCR) method, respectively. Results The Hardy-Weinberg equilibrium of single nucleotide polymorphism(SNP) was detected among controls (p = 0.2). Our results revealed that the TT genotype was more frequent in patients (22.6%) than controls (10%) while the CC genotype was more frequent in controls (47.3%) than patients (39.3%) (p = 0.01). The frequency of the T allele was significantly higher in patients than in controls (41.7 vs. 31.3%), while the C allele was more frequent in controls (p = 0.008). After adjustment for traditional risk factors, the association of the TT genotype with T1DM remained significant (TT vs. CC, odds ration [OR] = 3.2, 95% confidence interval [CI]: 1.4-7.4, p = 0.005). Power analysis of the data yielded a statistical power of 80% for the miR-196a2 rs11614913 with T1DM. Relative expression of miR-196a2 showed significant decrease in patients compared to controls (median = 0.09, 0.5, interquartile range [IQR] = 0.03-1.6, 0.1-2.1). However, miR-196a2 expression showed no significant difference between different rs11614913 genotypes (p = 0.5). Conclusions Our findings demonstrated that miR-196a rs11614913 is associated with T1DM and decreased expression of miR-196a2 may play a role in pathogenesis of T1DM.

Association of microRNAs genes polymorphisms with arthritis: a systematic review and meta-analysis.

Objective: To investigate whether microRNAs genes’ polymorphisms are associated with arthritis. Methods: The PubMed, Cochrane Library et al. were systematically searched to identify case–control studies, systematic reviews and meta-analyses. A meta-analysis was performed to calculate odds ratios (ORs), and confidence intervals (CIs) at 95% using fixed-effect model or random-effects model. Results: Twenty-two case–control studies involving 10489 participants fulfilled the inclusion criteria. MiR-146a rs2910164 (G/C) was not significantly associated with the risk of rheumatoid arthritis (RA) in any model. Significant associations were found between miR-146a rs2910164 (G/C) and the risk of psoriatic arthritis (PsA) in the heterozygous model and the dominant model. The heterozygous model showed a significant association between the miR-146a rs2910164 (G/C) polymorphism and ankylosing spondylitis (AS). And there was no significant association of miR-146a rs2910164 (G/C) with risk of juvenile rheumatoid arthritis (JRA) at any model. Additionally, there was a significant association of miR-499 rs3746444 (T/C) with risk of RA at two genetic models, and with a moderate heterogeneity. When subgroup analysis by ethnicity, significant associations were almost found between miR-499 rs3746444 (T/C) and the risk of RA in any model in Caucasian populations, and there is no heterogeneity. Conclusions: The association of miR-146a rs2910164 (G/C) with RA was not found. And there was a significant association between miR-146a rs2910164(G/C) and PsA or AS. MiR-499 rs3746444 (T/C) was associated with RA in Caucasian populations. These findings did not support the genetic association between miR-146a rs2910164 (G/C) and JRA susceptibility, as well as the association of miR-196a-2 rs11614913 (C/T), miR-146a rs2431697, miR-146a rs57095329, miR-149 rs22928323 with arthritis.

The effect of miR-146a rs2910164 and miR-149 rs2292832 polymorphisms on preeclampsia susceptibility.

Preeclampsia (PE) is a gestational disorder and genetic and epigenetic alterations can affect its pathogenesis. Some evidences showed that the altered expression of miRNAs in the placentas complicated by PE. The blood samples from 219 PE and 242 normotensive pregnant women and placental tissue samples from 111 PE and 119 normotensive women were collected. MiR-146a and miR-149 polymorphisms were genotyped in blood samples and placentas using PCR-RFLP method. The frequencies of maternal miR-146a rs2910164 GC and CC genotypes did not differ between PE and control groups. However, the miR-146a rs2910164 G/C polymorphism was associated with an increased risk of PE in dominant (OR 1.5, 95% CI 1-2.1; P = 0.04) and allelic (OR 1.4, 95% CI 1-1.9; P = 0.04) but not recessive models. Moreover, the maternal GC and CC genotypes were associated with a 1.9- and 3.4-fold increased risk of severe PE (OR 1.9, 95% CI 1.1-3.2; P = 0.02 and OR 3.4, 95% CI 1.3-9; P = 0.01, respectively) and miR-146a rs2910164 polymorphism could increase risk of severe PE in dominant and recessive models (OR 2.1, 95% CI 1.3-3.4; P = 0.004 and OR 2.6, 95% CI 1-6.7; P = 0.04). The placental miR-146a rs2910164 polymorphism was associated with PE susceptibility in dominant (OR 1.8, 95% CI 1.1-3; P = 0.03) and allelic models (OR 1.7, 95% CI 1.1-2.5; P = 0.02). The frequencies of maternal and placental miR-149 rs2292832 genotypes were not different between two groups and these genotypes were not associated with PE or severe PE risk. In conclusion, according to logistic regression analysis the maternal/placental miR-146a rs2910164 G/C polymorphism was associated with PE and/or severe PE risk.

Association of polymorphisms of miR-146a rs2910164 locus with clinical features of rheumatoid arthritis

To assess the association of single nucleotide polymorphisms (SNPs) of microRNA-146a (miR-146a) with clinical features of rheumatoid arthritis (RA). In 126 patients with RA and 102 matched healthy controls, SNPs of miR-146a rs2910164 locus were determined with a high-resolution melting method. The association of such polymorphisms with disease activity score in 28 joints (DAS28) and clinical features of RA was assessed. The distribution of SNPs of miR-146a rs2910164 among RA patients did not differ from that of the control group. No significant association was found between miR-146a rs2910164 polymorphism with DAS28. However, RA patients with a GG genotype had a greater chance to develop extra-articular manifestations (P<0.01). Polymorphisms of miR-146a rs2910164 locus is not an independent risk factor for RA, though its GG genotype may be associated with extra-articular manifestations of RA.

Association of MIR146A rs2910164 variation with a predisposition to sporadic breast cancer in a Pakistani cohort.

Single-nucleotide polymorphisms (SNPs) in genes coding for microRNAs (miRNAs) play a pivotal role in the progression of breast cancer (BC). We investigated the association of miR-146a rs2910164 GC polymorphism with the risk of BC in the Pakistani population. The miR-146a rs2910164 polymorphism was genotyped in 300 BC cases and 300 age- and gender-matched healthy controls using T-ARMS-PCR. Genotype and allele frequencies were calculated and the association between genotypes and the risk of BC was calculated by odds ratio (OR) and confidence interval (95%). A significant difference in genotypic frequencies (χ2 =63.10; P=<0.0001) and allelic frequencies (OR=0.3955 (0.3132-0.4993); P=<0.0001) was observed between cases and controls. Furthermore, we also found that miR-146 rs2910164 CC homozygote increased the risk of BC in the dominant (OR=0.2397 (0.1629-0.3526); P=0.0001; GG vs. GC + CC) and recessive (OR=2.803 (1.865-4.213); P=<0.0001; CC vs. GC + GG) inheritance models. In summary, miR-146a rs2910164 GC is significantly associated with BC in the Pakistani population. To our knowledge, this is the first study that assessed MIR146a rs2910164 G>C SNP in Pakistani population. By analyzing the secondary structure of MIR146A variant, a significant structural modification was noted. Study with a larger sample size is needed to further confirm of these findings.