miR-146a Rs2910164 Polymorphism Research Articles

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.

Associations between non-coding RNAs genetic polymorphisms with ovarian cancer risk: A systematic review and meta-analysis update with trial sequential analysis.

This systemic review and meta-analysis seeks to systematically analyze and summarize the association between non-coding RNA polymorphisms and ovarian cancer risk. We searched PubMed, Web of Science and CNKI for available articles on non-coding RNA polymorphisms in patients with ovarian cancer from inception to March 1, 2023. The quality of each study included in the meta-analysis was rated according to the Newcastle-Ottawa Scale.Odds ratios (ORs) with their 95% confidence intervals (95% CI) were used to assess associations. Chi-square Q-test combined with inconsistency index (I2) was used to test for heterogeneity among studies. Lastly, trial sequential analysis (TSA) software was used to verify the reliability of meta-analysis results, and in-silico miRNA expression were also performed. The meta-analysis was registered with PROSPERO (No. CRD42023422091). A total of 17 case-control studies with 18 SNPs were selected, including 2 studies with H19 rs2107425 and HOTAIR rs4759314, and 5 studies with miR-146a rs2910164 and miR-196a rs11614913. Significant associations were found between H19 rs2107425, miR-146a rs2910164, and miR-196a rs11614913 and ovarian cancer risk. Three genetic models of H19 rs2107425 (CT vs TT (heterozygote model): OR = 1.36, 95% CI = 1.22-1.52, P < .00001; CC + CT vs TT (dominant model): OR = 1.12, 95% CI = 1.02-1.24, P = .02; and CC vs CT + TT (recessive model): OR = 1.23, 95% CI = 1.16-1.31, P < .00001), 2 genetic models of miR-146a rs2910164 (allele model: OR = 1.75, 95% CI = 1.05-2.91, P = .03; and heterozygote model: OR = 0.33, 95% CI = 0.11-0.98, P = .05), 3 genetic models of miR-196a rs11614913 (allele model: OR = 0.70, 95% CI = 0.59-0.82, P < .0001; dominant model: OR = 1.62, 95% CI = 1.18-2.24, P = .0001; and recessive model: OR = 0.70, 95% CI = 0.57-0.87, P = .03) were statistically linked to ovarian cancer risk. Subgroup analysis for miR-146a rs2910164 was performed according to ethnicity. No association was found in any genetic model. The outcomes of TSA also validated the findings of this meta-analysis. This study summarizes that H19 rs2107425, miR-146a rs2910164, and miR-196a rs11614913 polymorphisms are significantly linked with the risk of ovarian cancer, and moreover, large-scale and well-designed studies are needed to validate our result.

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 of miR-149 T>C and miR-196a2 C>T Polymorphisms with Colorectal Cancer Susceptibility: A Case-Control Study.

The principal aim of the current study was to investigate the relationship between miR-149 T>C (rs2292832) and miR-196a2 C>T (rs11614913) small non-coding RNA polymorphisms and the risk of developing CRC in the Azerbaijani population. The study included 120 patients diagnosed with CRC and 125 healthy individuals. Peripheral blood samples were collected from all the subjects in EDTA tubes and DNA extraction was performed by salting out. Polymorphisms were determined using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. While comparing without gender distinction no statistical correlation was found between the heterozygous TC (OR = 0.66; 95% CI = 0.37-1.15; p = 0.142), mutant CC (OR = 1.23; 95% CI = 0.62-2.45; p = 0.550), and mutant C (OR = 1.03; 95% CI = 0.72-1.49; p = 0.859) alleles of the miR-149 gene and the CT (OR = 1.23; 95% CI = 0.69-2.20; p = 0.485), mutant TT (OR = 1.29; 95% CI = 0.67-2.47; p = 0.452), and mutant T (OR = 1.17; 95% CI = 0.82-1.67; p = 0.388) alleles of the miR-196a2 gene and the risk of CRC. However, among women, miR-149 TC (OR = 0.43; 95% CI = 0.19-1.01; p = 0.048) correlated with a reduced risk of CRC, whereas miR-196a2 CT (OR = 2.77; 95% CI = 1.13-6.79; p = 0.025) correlated with an increased risk of CRC. Our findings indicated that miR-149 T>C (rs2292832) might play a protective role in the development of CRC in female patients, whereas the miR-196a2 (rs11614913) polymorphism is associated with an increased risk of CRC in women in the Azerbaijani population, highlighting the importance of gender dimorphism in cancer etiology.

MiR-146a rs2910164 (G/C) polymorphism is associated with the development and prognosis of acute coronary syndromes: an observational study including case control and validation cohort

BackgroundPolymorphisms in microRNAs (miRNAs) play an important role in acute coronary syndromes (ACS). The purpose of this study was to assess the association of miR-146a rs2910164 and miR-34b rs4938723 polymorphisms with the development and prognosis of ACS and to explore the underlying mechanisms.MethodsA case–control study of 1171 subjects was included to determine the association of miR-146a rs2910164 and miR-34b rs4938723 polymorphisms with ACS risk. An additional 612 patients with different miR-146a rs2910164 genotypes, who underwent percutaneous coronary intervention (PCI) were included in the validation cohort and followed for 14 to 60 months. The endpoint was major adverse cardiovascular events (MACE). A luciferase reporter gene assay was used to validate the interaction of oxi-miR-146a(G) with the IKBA 3'UTR. Potential mechanisms were validated using immunoblotting and immunostaining.ResultsThe miR-146a rs2910164 polymorphism was significantly associated with the risk of ACS (Dominant model: CG + GG vs. CC, OR = 1.270, 95% CI (1.000–1.613), P = 0.049; Recessive model: GG vs. CC + CG, OR = 1.402, 95% CI (1.017–1.934), P = 0.039). Serum inflammatory factor levels were higher in patients with the miR-146a rs2910164 G allele than in those with the C allele. MiR-146a rs2910164 polymorphism in dominant model was associated with the incidence of MACE in post-PCI patients (CG + GG vs. CC, HR = 1.405, 95% CI (1.018–1.939), P = 0.038). However, the miR-34b rs4938723 polymorphism was not associated with the prevalence and prognosis of ACS. The G allele of miR-146a rs2910164 tends to be oxidized in ACS patients. The miRNA fractions purified from monocytes isolated from ACS patients were recognized by the 8OHG antibody. Mispairing of Oxi-miR-146a(G) with the 3'UTR of IKBA results in decreased IκBα protein expression and activation of the NF-κB inflammatory pathway. P65 expression was higher in atherosclerotic plaques from patients carrying the miR-146a rs2910164 G allele.ConclusionThe variant of miR-146a rs2910164 is closely associated with the risk of ACS in Chinese Han population. Patients carrying miR-146a rs2910164 G allele may have worse pathological change and poorer post-PCI prognosis, partly due to the oxidatively modified miR-146a mispairing with 3′UTR of IKBA and activating NF-κB inflammatory pathways.

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.

Commentary: Association between the miR-146a rs2910164 polymorphism and childhood acute lymphoblastic leukemia susceptibility in an Asian population.

GENERAL COMMENTARY article Front. Genet., 20 March 2023Sec. Statistical Genetics and Methodology Volume 14 - 2023 | https://doi.org/10.3389/fgene.2023.1134659

Pharmacogenetic Analysis of the MIR146A rs2910164 and MIR155 rs767649 Polymorphisms and Response to Anti-TNF Treatment in Patients with Crohn's Disease and Psoriasis.

The clinical heterogeneity regarding the response profile of the antitumor necrosis factor (anti-TNF) in patients with Crohn's disease (CD) and psoriasis (PsO) is attributed, amongst others, to genetic factors that influence the regulatory mechanisms which orchestrate the inflammatory response. Here, we investigated the possible associations between the MIR146A rs2910164 and MIR155 rs767649 variants and the response to anti-TNF therapy in a Greek cohort of 103 CD and 100 PsO patients. We genotyped 103 CD patients and 100 PsO patients via the PCR-RFLP method, utilizing the de novo formation of a restriction site for the SacI enzyme considering the MIR146A rs2910164, while Tsp45I was employed for the MIR155 rs767649 variant. Additionally, we investigated the potential functional role of the rs767649 variant, exploring in silico the alteration of transcription factor binding sites (TFBSs) mapped on its genomic location. Our single-SNP analysis displayed a significant association between the rare rs767649 A allele and response to therapy (Bonferroni-corrected p value = 0.012) in patients with PsO, a result further enhanced by the alteration in the IRF2 TFBS caused by the above allele. Our results highlight the protective role of the rare rs767649 A allele in the clinical remission of PsO, implying its utilization as a pharmacogenetic biomarker.

Association of rs2910164 in miR-146a with type 2 diabetes mellitus: A case-control and meta-analysis study.

ObjectiveSeveral studies have shown that miR-146a rs2910164 (C > G) is associated with type 2 diabetes mellitus (T2DM) susceptibility, but the results are still controversial. This study is divided into two parts, and one is to explore the relationship between miR-146a rs2910164 polymorphism and the genetic susceptibility of T2DM in Chinese Han population. Second, a meta-analysis on the basis of a larger sample size was used to determine whether this is a susceptibility gene for T2DM.MethodsA case–control study including 574 T2DM patients and 596 controls was used to evaluate the association of miR-146a rs2910164 polymorphism with the risk of T2DM in Chinese Han People. Then, we systematically searched studies investigating the correlation between miR-146a rs2910164 polymorphism and T2DM susceptibility published before April 2022 from PubMed, Web of Science, Wanfang, and China National Knowledge Infrastructure database, and a meta-analysis including six studies was carried out. The results were expressed by odds ratio (OR) and its 95% confidence interval (95% CI).ResultsIn a case–control study, we found that there were no statistical differences in genotype frequencies between T2DM and control group. Subgroup analysis showed that, compared with the CC genotype, CG + GG genotype was associated with a decreased risk of T2DM in the subgroup of individuals ≥ 65 years old (OR = 0.75; 95% CI: 0.58–0.98; P adjusted = 0.032) and BMI < 18.5 (OR = 0.16; 95% CI: 0.03–0.89; P adjusted = 0.037). In overall meta-analysis, significant heterogeneity was detected. No significant association between miR-146a rs2910164 polymorphism and T2DM was observed in all genetic models under random effects models. Subgroup analysis revealed that there was a significant difference in genotype frequencies between the T2DM and control group in recessive model (CC vs. CG + GG: OR = 1.79; 95% CI: 1.08–2.96; PQ = 0.307, I 2 = 4.0%) and homozygote model (CC vs. GG: OR = 1.79; 95% CI: 1.07–3.00; PQ = 0.216, I 2 = 34.7%) in Caucasians.ConclusionThe results of our study demonstrate that the miR-146a rs2910164 polymorphism might have ethnicity-dependent effects in T2DM and may be related to T2DM susceptibility in Caucasians.

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.

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.

Effect of miR-196a2 rs11614913 Polymorphism on Cancer Susceptibility: Evidence From an Updated Meta-Analysis.

Background: MiR-196a2 rs11614913 polymorphism has been studied in a wide range of cancers throughout the years. Despite a large number of epidemiological studies performed in almost all ethnic populations, the contribution of this polymorphism to cancer risk is still inconclusive. Therefore, this updated meta-analysis was performed to estimate a meticulous correlation between miR-196a2 rs11614913 variant and cancer susceptibility. Methods: A systematic study search was carried out using PubMed, ScienceDirect, CNKI, EMBASE, Scopus, and Google Scholar databases following PRISMA guidelines to find necessary literature up to December 15, 2021. Pooled odds ratios with corresponding 95% confidence intervals were estimated using RevMan 5.4 based on ethnicities, cancer types, control sources, and genotyping methods. Results: A total of 152 studies, including 120 135 subjects (53 818 patients and 66 317 controls; 140 studies, after removing studies that deviated from HWE: 51 459 cases and 62 588 controls), were included in this meta-analysis. Quantitative synthesis suggests that the miR-196a2 rs11614913 genetic variant is significantly correlated with the reduced risk of overall cancer in CDM2, CDM3, RM, and AM (odds ratio < 1 and P < .05). It is also observed from ethnicity-based subgroup analysis that rs11614913 polymorphism is significantly (P < .05) linked with cancer in the Asian (in CDM2, CDM3, RM, AM) and the African population (in CDM1, CDM3, ODM). Stratified analysis based on the cancer types demonstrated a significantly decreased correlation for breast, hepatocellular, lung, and gynecological cancer and an increased association for oral and renal cell cancer. Again, the control population-based subgroup analysis reported a strongly reduced correlation for HB population in CDM2, RM, and AM. A substantially decreased risk was also observed for other genotyping methods in multiple genetic models. Conclusions: MiR-196a2 rs11614913 variant is significantly correlated with overall cancer susceptibility. Besides, rs11614913 is correlated with cancer in Asians and Africans. It is also correlated with breast, gynecological, hepatocellular, lung, oral, and renal cell cancer.

No Association of MicroRNA-146a rs2910164 Polymorphism and Risk of Primary Gout Development in Chinese Han Populations: A Case-control Study.

Previous studies demonstrated that MicroRNA-146a (miR-146a) plays an important role in the regulation of autoinflammatory diseases including primary gout. The G/C polymorphism (rs2910164) in the precursor sequence of miR-146a caused its stem region to change from G: U to C: U,which can contribute to the susceptibility of human diseases. However, no genetic relevance studies of miR-146a gene polymorphisms to gout have been reported by now. The purpose of this study was to analyze the association between the miR-146a rs2910164 genetic polymorphism and the susceptibility of the Chinese Han population to primary gout. 1130 Chinese Han participants (including 606 primary gout patients and 524 gender and age-matched healthy control subjects) were recruited and the 5'exonuclease TaqMan® technology was used to perform miR-146a rs2910164 genotyping. After statistical analysis, no significant differences were observed between gout patients and healthy controls in genotype and allele frequency. Our results indicate that there is no evidence for the involvement of the miR-146a rs2910164 polymorphisms in susceptibility to primary gout in the Chinese Han population.

Association Between miR-146a rs2910164 Polymorphism and Breast Cancer Susceptibility: An Updated Meta-Analysis of 9545 Cases and 10030 Controls.

Several studies have reported a possible association of miR-146a rs2910164 polymorphism with Breast Cancer (BC) development. However, the correlation between this polymorphism and susceptibility to BC is under debate. The current meta-analysis was designed and performed to more conclusively evaluate the miR-146a rs2910164 polymorphism and its potential link to BC. Our team has selected eligible studies (published up to October 2, 2020) from several electronic databases, including Web of Science, PubMed, Scopus and Google Scholar. A total number of 9,545 BC cases and 10,030 controls extracted from 26 eligible articles were included in this study. We utilized pooled Odds Ratios (ORs) as well as 95% confidence intervals (95% CIs) under five genetic models for quantitative estimation of any possible association between miR-146a rs2910164 polymorphism and BC. Based on this meta-analysis, our findings suggest that there is no significant association between miR-146a rs2910164 polymorphism and BC risk. However, stratified analysis revealed that the rs2910164 polymorphism significantly increased the risk of BC in hospital-based studies using the homozygous genetic model (OR=1.37, 95%CI=1.01-1.86, p=0.043, CC vs. GG). Neither Asian nor Caucasian populations showed any significant association between rs2910164 polymorphism and BC susceptibility. In summary, our findings suggest that BC development is not associated with miR-146a rs2910164 polymorphism. However, larger ingenious future investigations might be needed for a more precise estimation of any association between miR-146a rs2910164 polymorphism and BC.

MiR-146a and miR-155 polymorphisms in Egyptian patients with Behcet's disease.

The current study was designed to analyze whether polymorphisms of miR-146a and miR-155 are related to Behçet's disease (BD) in the Egyptian population. A total of 96 unrelated BD patients and 100 healthy subjects were genotyped for miR-146a (rs2910164) and miR-155 (rs767649) using real-time polymerase chain reaction. The results showed significant elevation in the frequency of rs2910164 GG and CC genotypes in BD patients compared with controls (adjusted OR = 22.156, 95% CI: 4.728-103.818; p < 0.001 and adjusted OR = 40.358, 95% CI: 8.928-182.440; p < 0.001, respectively). Also, the rs2910164 G allele conferred a higher risk of developing BD (adjusted OR = 3.665, 95% CI: 2.013-6.671; p < 0.001). MiR-146a (rs2910164) polymorphism was a risk factor for susceptibility to BD in dominant, recessive and additive models of inheritance (all p < 0.001), while the miR-155 (rs767649) polymorphism was a risk factor in the recessive model only (p = 0.021). GG and CG genotypes of rs2910164 were associated with higher Behcet's disease current activity index (BDCAI) and ocular involvement compared with CC genotype (p = 0.005 and p = 0.004, respectively). Genotype AT of rs767649 was related to higher BDCAI (p = 0.026) compared with TT and AA genotypes. miR-146a (rs2910164) and miR-155 (rs767649) are likely to play an important role in the Egyptian population in development of BD and also influence disease severity.

The Association between Five Genetic Variants in MicroRNAs (rs2910164, rs11614913, rs3746444, rs11134527, and rs531564) and Cervical Cancer Risk: A Meta-Analysis.

The objective of this study was to conduct a meta-analysis to systematically summarize and investigate the association of miRNA-124 rs531564, miRNA-218 rs11134527, miRNA-146a rs2910164, miRNA-196a2 rs11614913, and miRNA-499 rs3746444 polymorphisms with cervical cancer. A systematic review was performed to identify relevant studies using Embase and PubMed databases. A chi-square-based Q-test combined with the inconsistency index (I2) was used to check the heterogeneity between studies. A total of six case-control studies on rs2910164 and rs11614913, 4 studies on rs3746444 and rs11134527, and three studies on rs531564 were included. No evidence of association was found between miR-146a rs2910164, miR-196a2 rs11614913, miRNA-499 rs3746444, and miR-218 rs11134527 polymorphisms and cervical cancer risk in all the genetic models. The miR-124 rs531564 polymorphism was associated with a statistically increased risk of cervical cancer in a homozygote model (CC vs. GG: OR = 2.87, 95% CI: 1.40-5.91, PH = 0.887), dominant model (GC/CC vs. GG: OR = 1.38, 95% CI: 1.07-1.80, PH = 0.409), and recessive model (CC vs. GC/GG: OR = 2.26, 95% CI: 1.58-3.23, PH = 0.979). However, this finding should be interpreted with caution for limited samples and heterogeneity. Large-scale and well-designed studies are needed to validate our result.

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.