miR-146a Polymorphisms Research Articles

The Relationship Between miR-196a2 Polymorphism and Colorectal Cancer Risk

ABSTRACT Objective MicroRNAs are small endogenous, non-coding, single-stranded posttranscriptional RNA molecules. The discovery of microRNAs has made new contributions to cancer diagnosis and treatment. These microRNAs reported as a responsible for colorectal cancer development with several epigenetic changes. In this study, it was aimed to evaluate the relationship between the polymorphism of miR-196a-2 polymorphism rs11614913 and colorectal cancer in Turkish population. Methods Two hundred colorectal cancer patient (124 colon cancer and 76 rectal cancer) and 240 health control individuals were included in our study, which was planned as a hospital based retrospective cohort study. MiR-196a2 polymorphism in peripheral blood samples has been determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) method. Significance of the results has been evaluated by using SPSS (20.0 SPSS Inc., Chicago, IL, USA.) statistical program. Results miR-196a2 C / C + C / T genotypes was found to be associated with the risk of colorectal cancer development (p: 0.001; OR: 2.04, 95% CI: 1.293-3.236). The subgroup analysis, showed that the C / C + C / T genotype increased the risk of colon cancer development 2.11 times (p: 0.016; 95% CI: 1.136-3.918) and rectal cancer 2.86 times (p: 0.011; 95% CI:1.242-6.592). The relationship between any clinicopathological features of colorectal cancer and the frequency of the C / C + C / T genotype of miR196a2 was not statistically significant (p> 0.05). Conclusion This study supports that miR-196a2's C / C + C / T genotypes is related with increased colorectal cancer development risk.

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.

Sex-dependent interaction of PTGS2 with miR-146a as risk factor for melanoma and the impact of sex hormones in gene expression in skin cells.

Gender disparity in melanoma is a complex issue where sex hormones could be engaged. Differences in genetic variations are important in understanding the mechanisms of sex disparity in melanoma. Post-transcriptional regulation of prostaglandin-endoperoxide synthase (PTGS2) mRNA occurs through a complex interplay of specific trans-acting RNA-binding proteins and microRNAs. MiR-146a is a key player in melanoma, modulating immune responses and tumor microenvironment (TME). Polymorphisms in PTGS2 gene rs20415G<C and miR-146a gene rs2910164G>C have been associated with an increased risk of melanoma. Epistasis between polymorphisms rs20415G<C and rs2910164G>C was investigated by genotyping 453 melanoma patients and 382 control individuals. The effects of testosterone and 17β-estradiol were analyzed in keratinocytes and two melanoma cell lines. The rs2910164GG showed a higher risk in the presence of the genotype rs20417CC in the male population. Testosterone and 17β-estradiol act differently on PTGS2 and miR-146a expression, depending on the cell type. Testosterone augments PTGS2 gene expression in keratinocytes and miR-146a in melanoma cells. While 17β-estradiol only increases miR-146a expression in HaCaT cells. The present study indicates a sex-specific relation between miR-146a and PTGS2 polymorphisms with melanoma cancer risk. Testosterone and 17β-estradiol act differently on the expression of PTGS2 and miR-146a depending on the skin cell type.

Role of Polymorphisms in MicroRNA-196a2, MicroRNA-499 and MicroRNA-146a for Prostate and Gastric Cancer Risk: An Updated Meta-analysis

Numerous studies have reported the polymorphisms in miR-196a2, miR-499 and miR-146a were associated with different types of cancers. However, the results have been inconsistent and varied. Therefore, we conducted a meta-analysis with the addition of the latest articles to explain the effect of these polymorphisms on Prostate (PCa) and Gastric cancer (GC). A total of 27 articles were recruited after a thorough literature analysis by two independent authors under the PRISMA guidelines in which 7 studies were related to PCa and 20 studies were of GC. We used STATA for performing the meta-analysis. The results from our analysis showed that miR-196a2 rs11614913 polymorphism is associated with PCa in allelic model in Asian population (CvsT: OR=1.207, 95%CI: 1.023-1.425, P=0.026), heterozygous model in Asian population (CvsT: OR=1.264, 95%CI: 1.008-1.585, P=0.042) while miR-499 rs3746444 is associated with PCa in allelic model overall population (AvsC: OR=1.201, 95%CI: 1.039 -1.388, P=0.013) and in Asian subjects (AvsC OR=1.23, 95%CI: 1.030-1.469, P=0.022). The miR-499 rs3746444 is also associated with GC in all four genetic models. Our results concluded that miR-196a2 rs11614913 and miR-499 rs3746444 may be involved in the development of PCa in Asian subjects while miR-499 rs3746444 may be related to GC prognosis

The impact of MIR196A2 and MIR423 genes polymorphisms on the development of type 2 diabetes mellitus in a sample of the Iraqi population

PurposeMicro-RNAs, play a significant role in regulating essential physiological processes by controlling post-transcriptional gene expression. Several disorders have been linked to variations in the miRNA genes that generate sequences of mature micro-RNA. The current research aims to determine if the genetic variations rs6505162; C > A in the MIR423 gene and rs11614913; T > C in the MIR196A2 gene are associated with type 2 diabetes mellitus (T2DM). MethodThe tetra-primers amplification refractory mutation system-polymerase chain reaction technique was used to identify these two single nucleotide polymorphisms (SNPs). ResultsThe allele frequency of MIR423- rs6505162; C > A SNP was 0.47 for the wild allele (A) and 0.53 for the mutant allele (C) in the control group, while in the patients group the frequency was 0.54 and 0.46 for the A and C alleles respectively. No association was discovered between this SNP and T2DM (O.R = 0.75, P = 0.47 for AC genotype, and O.R = 0.53, P = 0.15 for CC genotype). The wild type of MIR196A2 rs11614913; C > T SNP showed a 100% prevalence in the study subjects, thus this SNP has no association with T2DM as well. ConclusionThe current investigation demonstrates that the incidence of T2DM is not associated with the MIR196A2-rs11614913; C > T, and MIR423-rs6505162; C > A SNPs.

Effect of miR-146a polymorphism on lipoic acid therapy in patients with T2DM peripheral polyneuropthy.

For investigating the impact of miR-146a rs2910164 polymorphism on the therapeutic efficacy of lipoic acid therapy in patients with type 2 diabetes mellitus (T2DM) peripheral neuropathy (DPN). 106 T2DM-DPN patients in our hospital from Jan. 2020- 2022 were selected. The probe detection method was utilized to determine the polymorphism of the miR-146a rs2910164 gene in peripheral blood. All patients were treated with zinc sulfate for 3 weeks period. According to the treatment effect, 37 patients who were ineffective in treatment will be divided into an ineffective group, and 79 patients who were effective in treatment will be divided into an effective group. The condition of miR-146a gene peptides was analyzed after treatment in both groups. The motor nerve conduction velocity (MNCV), sensory nerve conduction velocity (SNCV), and Toronto Clinical Scoring System (TCSS) scores of the median nerve and common peroneal nerve with different genotypes were compared between the 2 sets. The genotype frequencies of alleles G, GG, and GC in the valid group were lower than those in the invalid group; After treatment, MNCV and SNCV of CC genotype median nerve and common peroneal nerve in DPN patients were higher than those before treatment; The TCSS scores of the three genotypes less than post-treatment. The above results showed statistically significant differences (P<0.05). Lipoic acid is influenced by the miR-146a polymorphism gene in the treatment of T2DM-DPN patients, with the CC genotype having a lower susceptibility and the best clinical treatment effect.

Mir146a Polymorphism in Gastric, Colon and Rectum Cancers

mir146a, a member of the microRNA family, plays an important role in the regulation of many biological pathways such as the regulation and differentiation of hematopoietic cells. The relationship between mir146a polymorphism and gastric, colon, rectum cancers have been investigated in Turkish population. Polymorphism in mir146a gene rs2961920 and rs2910164 have been determined in 212 patients (gastric: 73, colon:76 and rectum:63) and in 77 healthy controls by Real-Time PCR. Findings were evaluated by logistic regression and Khi (χ2) tests. The comparison of gastric, colon and rectum cancer patients and controls determined a statistically significant relationship for alcoholic drink consumption (p0.05). However, there was statistically significant relationship between this polymorphism and gastric cancer in GG+CG and CC genotypes when the gastric cancer patients and control group were evaluated for mir146a rs2910164 polymorphism (χ2: 5,49 p: 0,019). Similarly, there was statistically significant relationship between this polymorphism and gastric cancer in GG+CC and CG genotypes (χ2:5,39, p: 0,020). In this study, it is thought that by investigating the functions of microRNAs and their role in cancer, it may be promising in understanding the molecular pathology of cancer and in developing molecular targeted therapies.

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.

Impacts of Mir146a Genotypes on Bladder Cancer Risk in Taiwan.

The aim of this study was to investigate the association between single-nucleotide polymorphisms (SNPs) in mir146a and mir196a and bladder cancer (BLCA) risk in Taiwan. The genotypes of mir146a rs2910164 and mir196a rs11614913 were determined in 375 BLCA patients and 375 healthy controls using PCR-RFLP methodology, and their associations with BLCA risk were evaluated. The study also measured the serum expression level of mir146a using quantitative RT-PCR. The results showed that the distributions of CC, CG and GG genotypes of mir146a rs2910164 were 31.7%, 45.6% and 22.7% in the control group, and 21.9%, 44.3% and 33.8% in the case group, respectively. In logistic regression analyses, the heterozygous variant genotype CG carriers showed a marginally significant association with increased BLCA risk (OR = 1.41, 95% CI = 0.99-2.01), while the homozygous variant genotype GG carriers had a 2.17-fold increased risk of BLCA (OR = 2.17, 95%CI = 1.46-3.21). Moreover, carriers of the GG/CG genotypes had significantly higher serum levels of mir146a than those with the CC genotype (p < 0.0001), indicating a genotype-phenotype correlation. In contrast, mir196a rs11614913 was not associated with BLCA risk. Therefore, the genotypes of mir146a rs2910164 may serve as a useful biomarker for predicting the risk of BLCA.

Association of miR-196a2 and miR-27a polymorphisms with gestational diabetes mellitus susceptibility in a Chinese population.

MiR-196a2 and miR-27a play a key role in the regulation of the insulin signaling pathway. Previous studies have indicated that miR-27a rs895819 and miR-196a2 rs11614913 have a strong association with type 2 diabetes (T2DM), but very few studies have investigated their role in gestational diabetes mellitus (GDM). A total of 500 GDM patients and 502 control subjects were enrolled in this study. Using the SNPscan™ genotyping assay, rs11614913 and rs895819 were genotyped. In the data treatment process, the independent sample t test, logistic regression and chi-square test were used to evaluate the differences in genotype, allele, and haplotype distributions and their associations with GDM risk. One-way ANOVA was conducted to determine the differences in genotype and blood glucose level. There were obvious differences in prepregnancy body mass index (pre-BMI), age, systolic blood pressure (SBP), diastolic blood pressure (DBP) and parity between GDM and healthy subjects (P < 0.05). After adjusting for the above factors, the miR-27a rs895819 C allele was still associated with an increased risk of GDM (C vs. T: OR=1.245; 95% CI: 1.011-1.533; P = 0.039) and the TT-CC genotype of rs11614913-rs895819 was related to an increased GDM risk (OR=3.989; 95% CI: 1.309-12.16; P = 0.015). In addition, the haplotype T-C had a positive interaction with GDM (OR=1.376; 95% CI: 1.075-1.790; P=0.018), especially in the 18.5 ≤ pre-BMI < 24 group (OR=1.403; 95% CI: 1.026-1.921; P=0.034). Moreover, the blood glucose level of the rs895819 CC genotype was significantly higher than that of the TT and TC genotypes (P < 0.05). The TT-CC genotype of rs11614913-rs895819 showed that the blood glucose level was significantly higher than that of the other genotypes. Our findings suggest that miR-27a rs895819 is associated with increased GDM susceptibility and higher blood glucose levels.

Potential Impact of Polymorphisms in Toll-like Receptors 2, 3, 4, 7, 9, miR-146a, miR-155, and miR-196a Genes on Osteoarthritis Susceptibility.

Osteoarthritis (OA) is a progressive inflammatory disease of synovial joints and a leading cause of disability among adults. Inflammation-related genes, including genes for Toll-like receptors (TLRs), are tightly controlled by several microRNAs that, in addition to their pivotal role in the epigenetic regulation of target genes, are ligands for TLR activation and downstream signaling. Thus, we evaluated the association between OA risk and genetic variants in TLR2, TLR3, TLR4, TLR7, TLR9, and microRNAs that regulate TLRs signaling miR146a, miR155, and miR196a2. Our study group consisted of 95 surgically treated OA patients and a control group of 104 healthy individuals. Genetic polymorphisms were determined using TaqMan real-time PCR assays (Applied Biosystems). Adjusted logistic regression analysis demonstrated that polymorphisms in TLR4 rs4986790 (OR = 2.964, p = 0.006), TLR4 rs4986791 (OR = 8.766, p = 0.00001), and TLR7 rs385389 (OR = 1.579, p = 0.012) increased OA risk, while miR-196a2 rs11614913 (OR = 0.619, p = 0.034) was significantly associated with decreased OA risk. Our findings indicate that polymorphisms in the TLR4 and TLR7 genes might increase OA risk and suggest a novel association of miR-196a2 polymorphism with decreased OA susceptibility. The modulation of TLRs and miRNAs and their cross-talk might be an attractive target for a personalized approach to OA management.

Functional gene polymorphisms and expression alteration of selected microRNAs and the risk of various gastric lesions in Helicobacter pylori-related gastric diseases.

Background: Helicobacter pylori (Hp) persistent infection is an important pathogenic factor for a series of chronic gastric diseases from chronic gastritis to gastric cancer. Genetic and epigenetic abnormalities of microRNAs may play a vital role in the pathological evolution of gastric mucosa in Helicobacter pylori-related gastric diseases (HPGD). This study aimed to investigate the relationship between miR-146a, miR-196a2, miR-149, miR-499 and miR-27a gene single nucleotide polymorphisms (SNPs) and their expressions with pathological changes in gastric mucosa, and to further analyze the interactions between SNPs and Hp. Methods: Subjects in this study included patients diagnosed with HPGD and healthy controls. MiR-146a rs2910164, miR-196a2 rs11614913, miR-149 rs2292832, miR-499 rs3746444 and miR-27a rs895819 were genotyped by direct sequencing. Fluorescence quantitative PCR was used to detect microRNA expressions. Gene-gene and gene-environment interactions were evaluated by multifactor dimensionality reduction (MDR) method. Results: we found that frequency distribution of miR-196a2 rs11614913 CT genotype in gastric precancerous lesion (GPL) group and gastric cancer (GC) group was significantly higher than normal control (NOR) group [adjusted OR = 6.16, 95%CI (1.46-26.03); adjusted OR = 11.83, 95%CI (1.65-84.72), respectively]. CT genotype and C allele of miR-27a rs895819 were associated with increased risk of GC [adjusted OR = 10.14, 95%CI (2.25-45.77); adjusted OR = 3.71, 95%CI(1.46-9.44), respectively]. The MDR analysis results showed that the interaction between miR-196a2 rs11614913 and Hp was associated with the risk of GPL (p = 0.004). Meanwhile, the expression level of miR-196a2 in GC group was significantly higher than NOR, chronic inflammation (CI) and early precancerous lesion (EPL) groups among Hp-positive subjects. And expressions of miR-499 and miR-27a in GC group were both higher than EPL group. Also, miR-27a expression in GC group was higher than CI and gastric atrophy (GA) groups. Conclusion: miR-196a2 rs11614913 and miR-27a rs895819 may affect the genetic susceptibility to GPL or GC. MiR-196a2 rs11614913 and Hp have a synergistic effect in the occurrence and development of GPL. The up-regulation of miR-499, miR-196a2 and miR-27a expression caused by Hp infection may be an important mechanism of gastric carcinogenesis.

Evaluation of miR-146a (rs2910164) polymorphism in coronary artery disease: Case-control and silico analysis

As the most common cause of mortality, cardiovascular disease is a serious problem in the health system worldwide. The function of a small non-coding RNA, miR-146a, in inflammation and myocardial hypertrophy has been determined previously. In this experiment, we aim to assess the role of miR-146a polymorphism in cardiovascular disease. In this case-control study, 297 cardiovascular disease (CAD) patients and 306 healthy controls were enrolled. The polymerase chain reaction (PCR) and the restriction fragment length polymorphism (RFLP) were applied to determine the genotype of the miR-146a (rs2910164) SNP. The secondary structure of miR-146a and potential protein interactions of two alternative variants, C and G, were determined with in silico and computational analysis. Statistically, P < 0.05 was considered significant. The frequency of genotypes including CC, CG, and GG related to miR-146a (rs2910164) polymorphism showed no significant difference between CAD patients and controls (P = 0.928). The results of in silico and computational analysis reported that G and C-variants may support different RNA folding arrangements and promote different protein binding sites. However, miR-146a gene polymorphism (rs2910164) has no significant association with CAD in the study population.

Polymorphisms of miR-146a and susceptibility to ulcerative colitis risk: a case-control study

Considering the role of miR-146a in the control of inflammation, we assessed the importance of two miR-146a polymorphisms (rs2910164 and rs57095329) in the development and severity of ulcerative colitis (UC) in Iran. Genomic DNA of 150 cases with UC and 200 healthy individuals were genotyped using the PCR-RFLP technique. Statistical analyses were performed using Med Calc software. The miR-146a rs2910164 C allele was significantly associated with increased risk of UC. Individuals carrying the CC (rs2910164) were more than fourfold higher risk of UC relative to wild type homozygotes. The combined GC + CC genotypes were also associated with increased UC risk. We also found that the rs2910164 CC genotype was associated with a severe form of the disease However, the distribution of variant allele and genotypes of rs57095329 did not differ between the cases and controls. In conclusion, miR-146a rs2910164 polymorphism may play a role in UC. To confirm our findings, additional well-designed studies in diverse ethnic populations are required.

A genetic study of the association of six polymorphisms with rheumatoid arthritis in the Egyptian population

BackgroundRheumatoid arthritis (RA) is an autoimmune disease in which the immune system attacks the tissues of the joints by mistake. Different factors—either genetic or environmental—affect the development of the RA disease in patients. A lot of studies aimed to examine the genetic associations with this disease in different populations. This research aspires to perform a genetic association study between six single-nucleotide polymorphisms (SNPs) and RA disease in the Egyptian population with 49 controls and 52 patients. The SNPs that are included in this study are MIR146A rs2910164 (C:G), MIR499/MIR499A rs3746444 (T:C), MTMR3 rs12537(C:T), MIR155HG rs767649 (A:T), IRAK1 rs3027898 (A:C) and PADI4 rs1748033 (C:T).MethodsReal-time PCR with TaqMan allelic discrimination assay were both used to perform the genotyping. The Odds ratio models with 95% confidence interval were used to test the associations. The used models are multiplicative, recessive, dominant and co-dominant.ResultThe demonstrated results indicated that rs2910164 and rs12537 were associated with RA, while rs3746444 showed no association in all the tested models. The remaining SNPs were excluded as they didn't pass the Hardy–Weinberg equilibrium test.ConclusionThe MIR146A and MTMR3 polymorphisms showed susceptibility to RA. Moreover, MIR499/MIR499A had no role in the disease.

Early marker of ocular neurodegeneration in children and adolescents with type 1 diabetes: the contributing role of polymorphisms in mir146a and mir128a genes

BackgroundEarly ocular neurodegenerative signs of diabetic neuropathy (DN) can be found in children and adolescents with type 1 diabetes (T1D). No data are available on the potential role of polymorphisms in miRNAs genes in predisposing T1D subjects to these signs.AimsTo determine whether MIR146A rs2910164 and MIR128A rs11888095 polymorphisms are associated with early retinal and corneal neurodegenerative changes in pediatric patients with T1D.MethodsA total of 140 T1D children/adolescents underwent spectral domain-optical coherence tomography (SD-OCT) and in vivo confocal microscopy (IVCM) with measurement of retinal and corneal nerve fiber parameters. Risk factors for diabetes complications (diabetes duration, blood pressure, HbA1c) were recorded. Genotyping of rs2910164 and rs1188095 SNPs and genotype–phenotype association analysis were performed.ResultsThe C allele of rs2910164 in MIR146A was associated with higher values of IVCM parameters and minimum rim width (MRW) of the peripapillary region of optic nerve head measured in the retina, whereas the T allele of rs1188095 in MIR128A was associated with a significant impairment of them. Multiple regression analysis showed that MIR146A and MIR128A polymorphisms were significantly associated with corneal nerve fiber length (beta = 0.225 and − 0.204, respectively) and other IVCM parameters, independently from age, diabetes duration, HbA1c and systolic blood pressure percentile. Similar results were found for MRW (beta = 0.213 and − 0.286, respectively).ConclusionsThese results provide new insight into the genetic predisposition to DN showing that two polymorphisms in MIR146A and MIR128A genes could significantly contribute to the development of early ocular preclinical signs of DN.

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

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

Mir-146a genetic polymorphisms in systemic lupus erythematosus patients: Correlation with disease manifestations.

This study aimed to investigate the genetic polymorphisms of miR-146a SNPs (rs2910164, rs57095329, and rs2431697) in systemic lupus erythematosus (SLE) patients and their association with clinical manifestations. The implication of SNPs on miR-146a expression level was also evaluated. SLE patients (113) and healthy controls (104) were registered in this study. The miR-146a SNPs were genotyped by polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP). Quantitative real-time PCR was used to measure the miR-146a expression in peripheral blood mononuclear cells (PBMCs). Our results showed that the genotype frequency of miR-146a SNPs didn't deviate significantly from the Hardy–Weinberg equilibrium (HWE). The AG genotype and G allele of miR-146a (rs57095329 A/G) might be considered a risk factor for the disease (OR = 2.27; CI: 0.78–6.57 and OR: 2.35; CI: 0.79–6.92 for AG genotype and G allele, respectively). Although, no statistical significance in the distribution of miR-146a SNPs (rs2910164, rs57095329, and rs2431697) was found, indicating the lack of association between the three SNPs and SLE susceptibility. Significantly, the higher frequency of the AA genotype of miR-146a (rs57095329) was associated with pancytopenia (P < 0.05), while the CT genotype of miR-146a (rs2431697) was associated (P < 0.05) with the antiphospholipid syndrome (APS). SLE patients had significantly higher levels of miR-146a compared to controls (P < 0.05). Elevation of miR-146a was independent of any SNP genotypes. In conclusion, this pilot study shows no association between miR-146a SNPs in our population group and susceptibility to lupus. Studies concerning other miRNAs in larger sample sizes are essential for a better understanding of their role in susceptibility to SLE disease.

Association of Polymorphisms in miR146a, an Inflammation-Associated MicroRNA, with the Risk of Idiopathic Recurrent Spontaneous Miscarriage: A Case-Control Study.

It has been established that microRNAs (miRNAs) are involved in the regulation of immune responses and serve as biomarkers of inflammatory diseases as well as recurrent spontaneous miscarriage (RSM). Herein, we aimed to study the relationship between three functional miR146a gene polymorphisms with idiopathic RSM (IRSM) susceptibility. We recruited 161 patients with IRSM and 177 healthy women with at least one live birth and without a history of abortion. Genotyping was performed using RFLP-PCR and ARMS-PCR methods. We found that the rs6864584 T/C decreased the risk of IRSM under dominant TT+TC vs. CC (OR = 0.029) and allelic C vs. T (OR = 0.028) contrast models. Regarding rs2961920 A/C and rs57095329 A/G polymorphisms, the enhanced risk of IRSM was observed under different genetic contrasted models, including the codominant CC vs. AA (OR = 2.81 for rs2961920) and codominant GG vs. AA (OR = 2.36 for rs57095329). After applying a Bonferroni correction, haplotype analysis revealed a 51% decreased risk of IRSM regarding the ACA genotype combination. This is the first study reporting that miR146a rs57095329 A/G, rs2961920A/C, and rs6864584 T/C polymorphisms are associated with the risk of IRSM in a southern Iranian population. Performing replicated case-control studies on other ethnicities is warranted to outline the precise effects of the studied variants on the risk of gestational trophoblastic disorders.

Association study of miR-149, miR-196a2, and miR-499a polymorphisms with coronary artery aneurysm of Kawasaki disease in southern Chinese population.

BackgroundAccumulating evidence suggests that several microRNA (miRNA) polymorphisms are closely associated with disease susceptibility or progression, such as in Kawasaki disease (KD). Our previous studies revealed the association of miR‐149 rs2292832 T>C and miR‐196a2 rs11614913 C>T polymorphisms with KD susceptibility. The present study further focused on the relationship between three miRNA polymorphisms (miR‐149 rs2292832 T>C, miR‐196a2 rs11614913 C>T and miR‐499a rs3746444 A>G) and the risk of coronary artery aneurysm (CAA) in southern Chinese KD patients.MethodsWe evaluated 318 KD patients with CAAs and 784 patients without CAAs. TaqMan assays were used to estimate genotyping and analyze the relationship between miRNA polymorphisms (miR‐149 rs2292832 T>C, miR‐196a2 rs11614913 C>T and miR‐499a rs3746444 A>G) and risk associations of CAA by odds ratios (ORs) and 95% confidence intervals (CIs).ResultsWe found that the miR‐149 rs2292832 TC/CC genotype increased the CAA risk (adjusted OR = 1.53, 95% CI = 1.15–2.03, p = 0.003 for TC, adjusted OR = 1.63, 95% CI = 1.08–2.47, p = 0.021 for CC), whereas the miR‐499a rs3746444 AG genotype decreased the CAA risk in KD patients (adjusted OR = 0.33, 95% CI = 0.25–0.45 p ≤ 0.001). Moreover, patients carrying two or three of these single nucleotide polymorphism (SNP) genotypes (rs2292832 TC/CC and rs11614913 TT and rs3746444 AA) had a higher risk for CAA than those who harbored only zero or one of these SNP genotypes.ConclusionsOur results demonstrated that the miR‐149 rs2292832 T>C polymorphism increased the risk of CAA in KD patients and that the miR‐499a rs3746444 A>G polymorphism decreased the risk of CAA in KD patients. Further studies with larger sample sizes and different centers are needed to confirm the findings of the present study.