BACKGROUND & AIMS: :MicroRNAs (miRNAs) are small non-coding RNA molecules, which act as post-transcriptional regulators of gene expression and have been implicated in initiation, progression and treatment outcome of diverse cancers. Single nucleotide polymorphisms (SNPs), as the most common type of genetic variation, also exist in miRNA genes and can lead to alteration in miRNA expression resulting in diverse functional consequences. Emerging studies have evaluated the association of miRNA SNPs with cancer risk, but the results remain inconclusive. To assess the relationship between miRNA SNPs and cancer risk, we performed a meta-analysis of 18 studies involving 20660 subjects for miR-146a rs2910164 polymorphism and 21 studies involving 26,018 subjects for miR-196a2 rs11614913 polymorphism. As for rs2910164, no significant association of cancer risk was found in the overall analysis. In subgroup analysis by cancer type, ethnicity, source of controls and sample size, significant association of cancer risk was mainly found in papillary thyroid carcinoma, primary liver cancer, cervical cancer, Caucasian population and small sample size studies. For rs11614913, significant results were found in all the tested genetic models and T allele or its carriers were associated with decreased cancer risk in overall analysis (T vs. C: OR = 0.888, 95% CI 0.84-0.938; TT+TC vs. CC: OR = 0.897, 95% CI 0.828-0.971). In stratified analysis by cancer type and ethnicity, significant association of cancer risk was observed in breast cancer, lung cancer, colorectal cancer and Asian population, but not in Caucasian population. During further stratified analysis by source of controls and sample size, results similar to those of overall analysis were found in all of the subgroups. Taken together, our results indicated that miR-196a2 rs11614913 T variant probably contribute to decreased susceptibility to cancer. However, limited evidence was found for association of miR-146a rs2910164 with cancer risk, and further well-designed studies with large sample size will be necessary to validate the effect of miR-146a rs2910164 on cancer susceptibility.

背景与目标： ：MicroRNA（miRNA）是小的非编码RNA分子，可作为基因表达的转录后调节剂，并与多种癌症的发生，进展和治疗结果有关。单核苷酸多态性（SNP）是最常见的遗传变异类型，也存在于miRNA基因中，并可导致miRNA表达发生变化，从而导致多种功能后果。新兴研究已经评估了miRNA SNP与癌症风险之间的关系，但结果尚无定论。为了评估miRNA SNP与癌症风险之间的关系，我们对18项涉及20660名miR-146a rs2910164多态性受试者的研究和21项涉及26018名miR-196a2 rs11614913多态性受试者的研究进行了荟萃分析。至于rs2910164，在总体分析中未发现明显的癌症风险关联。在按癌症类型，种族，控制源和样本量进行的亚组分析中，癌症风险的显着相关性主要发现于甲状腺乳头状癌，原发性肝癌，宫颈癌，高加索人群和小样本量研究中。对于rs11614913，在所有测试的遗传模型中均发现了显着结果，并且在整体分析中T等位基因或其携带者与降低癌症风险相关（T vs. C：OR = 0.888，95％CI 0.84-0.938； TT TC vs. CC ：OR ＝ 0.897，95％CI 0.828-0.971）。在按癌症类型和种族进行的分层分析中，在乳腺癌，肺癌，大肠癌和亚洲人群中观察到了癌症风险的显着关联，而在白种人人群中则没有。在按控制源和样本量进行的进一步分层分析中，在所有亚组中均发现了与总体分析相似的结果。综上所述，我们的结果表明miR-196a2 rs11614913 T变体可能有助于降低对癌症的敏感性。然而，发现miR-146a rs2910164与癌症风险相关的证据有限，因此，有必要进一步设计良好的大样本研究来验证miR-146a rs2910164对癌症易感性的影响。

BACKGROUND & AIMS: BACKGROUND:It has been reported that two single nucleotide polymorphisms (SNPs) rs2910164 in miRNA-146a and rs3746444 in miRNA-499 might be associated with the susceptibility to rheumatoid arthritis (RA). Owing to mixed and inconclusive results, we conducted a meta-analysis to systematically summarize and clarify the association between the two SNPs and RA risk. METHODOLOGY/MAIN RESULTS:A systematic search of studies on the association of two SNPs with susceptibility to RA was conducted in PubMed and Embase. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to pool the effect size. A total of 6 case-control studies on rs2910164 and 3 studies on rs3746444 were included. Though no evidence of association was found between rs2910164 polymorphism and RA risk in all the genetic models, a trend of reduced risk could be drawn. (C versus G: OR=0.93, 95% CI 0.82-1.05; GC versus GG: OR=0.89, 95% CI 0.73-1.10; CC versus GG: OR=0.84, 95% CI 0.64-1.10; GC/CC versus GG: OR=0.89, 95% CI 0.73-1.08; CC versus GC/GG:OR=0.94, 95% CI 0.77-1.14). A significant increased risk of RA was observed in the rs3746444 polymorphism in homozygote comparison, recessive comparison, and allele comparison, but there was insufficient data to fully confirm the association of RA and rs3746444 in miRNA-499. CONCLUSIONS:MiRNA-146a rs2910164 polymorphism is not associated with RA risk, while miRNA-499 rs3746444 polymorphism is correlated with RA risk. However, the results of miRNA-499 rs3746444 should be interpreted with caution due to limited sample and heterogeneity. Large-scale and well-designed studies are needed to validate our findings.

背景与目标： 背景：据报道，miRNA-146a中的两个单核苷酸多态性（SNP）rs2910164和miRNA-499中的rs3746444可能与类风湿关节炎（RA）的易感性有关。由于结果混杂且不确定，我们进行了荟萃分析，系统地总结和阐明了两个SNP与RA风险之间的关系。
方法/主要结果：在PubMed和Embase中对两种SNP与RA敏感性相关性的研究进行了系统的研究。使用赔率（OR）和95％置信区间（95％CI）合并效应量。总共包括6项针对rs2910164的病例对照研究和3项针对rs3746444的研究。尽管在所有遗传模型中都没有发现rs2910164多态性与RA风险之间存在关联的证据，但可以得出降低风险的趋势。 （C vs G：OR = 0.93，95％CI 0.82-1.05; GC vs GG：OR = 0.89，95％CI 0.73-1.10; CC vs GG：OR = 0.84，95％CI 0.64-1.10; GC / CC vs. GG：OR = 0.89，95％CI 0.73-1.08； CC vs
GC / GG：OR ＝ 0.94，95％CI 0.77-1.14）。在纯合子比较，隐性比较和等位基因比较中，在rs3746444多态性中观察到RA的风险显着增加，但是没有足够的数据来充分证实miRNA-499中RA和rs3746444的关联。
结论：miRNA-146a rs2910164多态性与RA风险无关，而miRNA-499 rs3746444多态性与RA风险相关。但是，由于样品和异质性有限，应谨慎解释miRNA-499 rs3746444的结果。需要进行大规模且设计合理的研究以验证我们的发现。

BACKGROUND & AIMS: :MicroRNAs are short non-coding RNAs that regulate gene expression by RNA interference. Oral squamous cell carcinoma (OSCC) is a prevalent malignancy worldwide. miR-146a has been reported to regulate Toll-like receptors and cytokine signaling, which are both crucial for inflammation and oncogenesis. This study identifies that areca nut extract, TNFα and TGFβ up-regulates miR-146a in OSCC cells. The increased expression of miR-146a enhanced the oncogenicity of OSCC cells. In addition, a G to C polymorphism (rs2910164), which is located in the pre-miR-146a and has been associated with functional alterations in miR-146a, was significantly more prevalent among OSCC patients having more advanced nodal involvement. Our analysis also suggested a higher miR-146a expression in OSCC tissues of patients carrying C polymorphism. The present study concluded a higher prevalence of the pre-mir-146a C-variant was associated with OSCC progression in patients with this disease.

背景与目标： ：MicroRNA是短的非编码RNA，可通过RNA干扰调节基因表达。口腔鳞状细胞癌（OSCC）是世界范围内普遍存在的恶性肿瘤。据报道，miR-146a调节Toll样受体和细胞因子信号传导，这对于炎症和肿瘤的发生均至关重要。这项研究确定了槟榔提取物，TNFα和TGFβ上调OSCC细胞中的miR-146a。 miR-146a表达的增加增强了OSCC细胞的致癌性。此外，位于miR-146a前的G到C多态性（rs2910164）与miR-146a的功能改变有关，在结节受累程度更高的OSCC患者中明显更为普遍。我们的分析还表明，携带C基因多态性的OSCC组织中miR-146a的表达较高。本研究得出结论，该疾病患者中mir-146a前C变体的较高患病率与OSCC进展相关。

BACKGROUND & AIMS: 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.

背景与目标： 背景：许多研究调查了miR-146a rs2910164多态性与缺血性心脑血管疾病风险之间的关系。但是，结果不一致。
方法：我们在PubMed，EMBASE，Cochrane图书馆，Web of Science，中国国家知识基础设施，VIP和Wanfang数据库中进行搜索，以进行适当的研究。计算具有95％置信区间（CI）的几率（OR）以评估关联。进行异质性，敏感性和发表偏倚来衡量我们研究结果的稳健性。所有分析均基于先前发表的研究，因此无需获得伦理学批准和患者同意。
结果：我们进行了荟萃分析，以评估miR-146a rs2910164多态性与缺血性心脑血管疾病风险之间的关系。总共鉴定了26项相关研究，涉及11,602例病例和14,016例对照，并将其纳入我们的荟萃分析。考虑到全局分析的异质性后，我们推断在所有遗传模型中，rs2910164多态性与冠心病（CHD）的较低风险显着相关。此外，还发现在大样本亚组分析中，miR-146a rs2910164多态性与缺血性心脑血管疾病的低风险相关。
结论：这些结果表明，miR-146a rs2910164多态性与缺血性心脑血管的低风险显着相关。可能建议将miR-146a rs29101164作为缺血性心脑血管疾病易感性的预测指标。

BACKGROUND & AIMS: OBJECTIVE:Circulating miR-146a is aberrantly expressed in patients with type 2 diabetes (T2D), probably resulting from gene polymorphisms. However, the role of polymorphism rs2910164 in T2D pathogenesis remains controversial. Thus, we designed a meta-analysis to investigate the association between rs2910164 and T2D. METHODS:PubMed and Embase were searched for eligible papers in English published through September 2, 2019. Random or fixed effect models were used to determine risk estimates according to heterogeneities. RESULTS:Four studies, involving 2,069 patients and 1,950 controls, were included. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to pool the effect size. The pooled ORs and 95% CIs were 1.501 (0.887-2.541), 1.102 (0.931-1.304), 1.276 (0.900-1.811), 1.204 (0.878-1.652), 1.238 (0.880-1.740), and 1.350 (0.904-2.016) under the homozygote, heterozygote (CG vs. GG and CC vs. CG), dominant, allele, and recessive models, respectively. Heterogeneity was detected in most genetic models, with subgroup analyses performed by ethnicity, genotyping method, and disease duration. The co-dominant model was determined to be the most appropriate genetic model. CONCLUSIONS:Our findings suggested that polymorphism rs2910164 is not correlated with T2D susceptibility. However, the results should be interpreted with caution because of confounding factors.

背景与目标： 目的：在2型糖尿病（T2D）患者中异常表达循环miR-​​146a，可能是由于基因多态性所致。然而，多态性rs2910164在T2D发病机理中的作用仍存在争议。因此，我们设计了一项荟萃分析来研究rs2910164与T2D之间的关联。
方法：检索PubMed和Embase截至2019年9月2日以英文发表的合格论文。根据异质性，使用随机或固定效应模型确定风险估计。
结果：四项研究包括2,069名患者和1,950名对照。使用赔率（OR）和95％置信区间（95％CI）合并效应量。合并的OR和95％CI为1.501（0.887-2.541），1.102（0.931-1.304），1.276（0.900-1.811），1.204（0.878-1.652），1.238（0.880-1.740）和1.350（0.904-2.016）在纯合子，杂合子（CG vs. GG和CC vs. CG），显性，等位基因和隐性模型下。在大多数遗传模型中均检测到异质性，并通过种族，基因分型方法和疾病持续时间进行了亚组分析。共主导模型被确定为最合适的遗传模型。
结论：我们的发现提示rs2910164多态性与T2D易感性无关。但是，由于存在混杂因素，应谨慎解释结果。

BACKGROUND & AIMS: PURPOSE:Emerging evidence has shown that single nucleotide polymorphisms occurred in microRNAs may contribute to the development of colorectal cancer (CRC). rs2910164 in miR-146a and rs11614913 in miR-196a2 are suggested to be associated with the susceptibility to CRC, but individually published studies revealed inconclusive results. To systematically summarize the possible correlationship between these polymorphisms and CRC risk, we performed this meta-analysis. METHODS:We retrieved the relevant articles of the associations between these two microRNA polymorphisms and susceptibility to CRC for the period up to July 1, 2013. A total of seven articles were identified with 2,143 cases and 2,457 controls for miR-146a rs2910164, 1,594 cases and 2,252 controls for miR-196a2 rs11614913. Odds ratio and 95 % confidence interval were calculated to investigate the strength of the association. RESULTS:The pooled analysis showed that miR-146a rs2910164 did not reveal any correlation with CRC susceptibility. However, a decreased risk was observed between miR-196a2 rs11614913 and CRC in all genetic models. CONCLUSION:Our current meta-analysis demonstrates that miR-196a2 rs11614913 most likely contributes to decreased risk of CRC, whereas miR-146a rs2910164 may not be associated with the susceptibility to CRC.

背景与目标： 目的：新兴证据表明，microRNA中发生的单核苷酸多态性可能有助于结直肠癌（CRC）的发展。有人认为miR-146a中的rs2910164和miR-196a2中的rs11614913与CRC的易感性有关，但个别发表的研究显示了不确定的结果。为了系统地总结这些多态性与CRC风险之间可能的相关性，我们进行了这项荟萃分析。
方法：我们检索了截至2013年7月1日这两种microRNA多态性与CRC敏感性之间相关性的相关文章。共鉴定了7篇文章，其中miR-146a rs2910164的2,143例和2,457例对照，1,594例以及针对miR-196a2 rs11614913的2,252个控件。计算赔率和95％的置信区间以研究关联的强度。
结果：汇总分析表明，miR-146a rs2910164与CRC敏感性没有任何相关性。但是，在所有遗传模型中，miR-196a2 rs11614913与CRC之间的风险均降低。
结论：我们目前的荟萃分析表明，miR-196a2 rs11614913最有可能导致CRC风险降低，而miR-146a rs2910164可能与CRC易感性无关。

BACKGROUND & AIMS: :The aim of the present study was to investigate the association of single nucleotide polymorphisms (SNP) of the microRNA-146a (miR-146a) genes with the risk of nonsmall cell lung cancer (NSCLC). The genotyping of miR-146a rs2910164 polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The results showed that CC genotype and C allele distribution in the NSCLC patient were significantly higher than that of the controls (P=0.03 and 0.03, respectively). No significant differences were found between the two subgroups when stratified by clinical characteristics including age, sexual, smoke status, histological type, lymph node metastasis and clinical stage. In addition, the expression of miR-146a was detected by the Taqman real-time PCR. It demonstrated that the miR-146a expression was significantly decreased in NSCLC patients compared with that of nonmalignant lung tissues (P=0.01). In addition, the miR-146a expression of CC genotypes subgroup was significantly decreased than of GC/GG genotype subgroup in tumor tissues (P=0.0022). It confirmed that the SNP rs2910164 could functionally affect the miR-146a expression levels. In conclusion, it showed that the rs2910164 polymorphism of miR-146a is associated with the risk of NSCLC in the Chinese population.

背景与目标： ：本研究的目的是研究microRNA-146a（miR-146a）基因的单核苷酸多态性（SNP）与非小细胞肺癌（NSCLC）风险的关系。通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）检测miR-146a rs2910164多态性的基因型。结果表明，NSCLC患者的CC基因型和C等位基因分布显着高于对照组（分别为P = 0.03和0.03）。在按年龄，性别，吸烟状况，组织学类型，淋巴结转移和临床阶段等临床特征进行分层时，在两个亚组之间没有发现显着差异。另外，通过Taqman实时PCR检测到miR-146a的表达。这表明与非恶性肺组织相比，NSCLC患者中的miR-146a表达显着降低（P = 0.01）。此外，在肿瘤组织中CC基因型亚组的miR-146a表达明显低于GC / GG基因型亚组（P = 0.0022）。它证实了SNP rs2910164可以在功能上影响miR-146a的表达水平。总之，它表明miR-146a的rs2910164多态性与中国人群发生NSCLC的风险有关。

BACKGROUND & AIMS: Background:MiR-146a, an effector mediator, targets Notch-1 and regulates the innate and adaptive immune systems response. Recently, we reported that Notch-1 signaling plays a key role in macrophage polarization and response during infection. We employed Mycobacterium avium paratuberculosis (MAP) infection in Crohn's disease (CD) as a model to demonstrate the role of Notch-1/IL-6 signaling on MCL-1 based apoptosis and intracellular MAP infection and persistence. This study was designed to investigate the impact of polymorphisms in miR146a on the immune response and infection in our MAP-CD model. Methods:We determined the incidence of miR-146a rs2910164 G > C in 42 blood samples from clinical CD patients and controls. We also measured the effect of rs2910164 on expression of Notch-1 and IL-6, and plasma IL-6 protein levels in our study group. Finally, we analyzed the blood samples for MAP DNA and studied any correlation with miR-146a polymorphism. Samples were analyzed for statistical significance using unpaired tow-tailed t-test, unpaired two-tailed z-score and odds ratio. P < 0.05 considered significant. Results:MiR-146a rs2910164 GC was detected at a higher incidence in CD (52.6%) compared to healthy controls (21.7%) rs2910164 GC Heterozygous polymorphism upregulated Notch-1 and IL-6, by 0.9 and 1.7-fold, respectively. As expected, MAP infection was detected more in CD samples (63%) compared to healthy controls (9%). Surprisingly, MAP infection was detected at a higher rate in samples with rs2910164 GC (67%) compared to samples with normal genotype (33%). Conclusions:The data clearly associates miR-146a rs2910164 GC with an overactive immune response and increases the risk to acquire infection. The study is even more relevant now in our efforts to understand susceptibility to SARS-CoV-2 infection and the development of COVID-19. This study suggests that genetic variations among COVID-19 patients may predict who is at a higher risk of acquiring infection, developing exacerbating symptoms, and possibly death. A high scale study with more clinical samples from different disease groups is planned.

背景与目标： 背景：效应子介体MiR-146a靶向Notch-1，并调节先天性和适应性免疫系统反应。最近，我们报道了Notch-1信号在感染过程中在巨噬细胞极化和反应中起关键作用。我们在克罗恩病（CD）中采用鸟分枝杆菌副结核分枝杆菌（MAP）感染作为模型来证明Notch-1 / IL-6信号在基于MCL-1的细胞凋亡以及细胞内MAP感染和持久性中的作用。这项研究旨在调查miR146a多态性对我们MAP-CD模型中免疫反应和感染的影响。
方法：我们确定了42例临床CD患者和对照组血液样本中miR-146a rs2910164 G> C的发生率。我们还测量了rs2910164对Notch-1和IL-6表达以及血浆IL-6蛋白水平的影响。最后，我们分析了血液样本中的MAP DNA，并研究了与miR-146a多态性的任何相关性。使用不成对的拖尾t检验，不成对的两尾z得分和比值比分析样本的统计显着性。 P <0.05被认为是显着的。
结果：与健康对照组（21.7％）相比，检测到MiR-146a rs2910164 GC的CD发生率更高（52.6％）rs2910164 GC杂合多态性分别将Notch-1和IL-6上调0.9倍和1.7倍。正如预期的那样，与健康对照组（9％）相比，在CD样品（63％）中检测到了MAP感染。令人惊讶的是，与具有正常基因型的样本（33％）相比，使用rs2910164 GC的样本（67％）以更高的比率检测到MAP感染。
结论：这些数据清楚地将miR-146a rs2910164 GC与过度活跃的免疫反应相关联，并增加了获得感染的风险。现在，这项研究与我们了解SARS-CoV-2感染的易感性和COVID-19的发展的努力更加相关。这项研究表明，COVID-19患者之间的遗传变异可以预测谁更容易感染，出现恶化症状甚至死亡。计划进行大规模研究，其中包括来自不同疾病组的更多临床样品。

BACKGROUND & AIMS: :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.

背景与目标： ：编码微RNA（miRNA）的基因中的单核苷酸多态性（SNP）在乳腺癌（BC）的进展中起关键作用。我们调查了miR-146a rs2910164 GC多态性与巴基斯坦人群BC风险的关系。使用T-ARMS-PCR在300 BC病例和300个年龄和性别匹配的健康对照中对miR-146a rs2910164多态性进行了基因分型。计算基因型和等位基因频率，并通过比值比（OR）和置信区间（95％）计算基因型与BC风险之间的关联。在病例和对照之间观察到基因型频率（χ2= 63.10; P = <0.0001）和等位基因频率（OR = 0.3955（0.3132-0.4993）; P = <0.0001）有显着差异。此外，我们还发现miR-146 rs2910164 CC纯合子增加了显性（OR = 0.2397（0.1629-0.3526）; P = 0.0001; GG vs.GC CC）和隐性（OR = 2.803（1.865-4.213）的BC风险。 ）; P = <0.0001; CC与GC GG）继承模型。总之，在巴基斯坦人口中，miR-146a rs2910164 GC与BC显着相关。据我们所知，这是第一项评估巴基斯坦人群中MIR146a rs2910164 G> C SNP的研究。通过分析MIR146A变体的二级结构，注意到了显着的结构修饰。需要进行更大样本量的研究以进一步证实这些发现。

BACKGROUND & AIMS: :Alteration in microRNA-146a (miRNA-146a) expression is an important event in the pathogenesis of many human diseases. MiRNA-146a rs2910164 is a functional polymorphism that showed association with several diseases. Metabolic syndrome is an aggregation of multiple risk factors including impaired glucose tolerance, increased highdensity lipoprotein, abdominal obesity, and high blood pressure. The aim of this study was to assess the relation of miRNA-146a rs2910164 with metabolic syndrome and its component traits in Egyptian women from the Suez Canal area. The study included 100 healthy female subjects and 100 metabolic syndrome patients. The component traits of metabolic syndrome were determined and the genotypes of the polymorphisms were assessed using the polymerase chain reaction-restriction fragment length polymorphism technique using the restriction enzyme Hpy188I. The rare C allele had a significantly higher frequency in metabolic syndrome patients (P = 0.013). The heterozygote GC and the rare CC genotypes showed a significant increase in body mass index, waist circumference, triglycerides, total cholesterol, low-density lipoprotein, systolic and diastolic blood pressure. The GC genotype was associated with higher fasting blood glucose, fasting serum insulin and insulin resistance. The carriers of CC genotype had significantly lower HDL compared with the GG genotype carriers. In conclusion, The C allele of miRNA-146a rs2910164 showed positive association with increased susceptibility to metabolic syndrome and its phenotypes in the study population.

背景与目标： ：microRNA-146a（miRNA-146a）表达的改变是许多人类疾病发病机理中的重要事件。 MiRNA-146a rs2910164是一种功能性多态性，显示与多种疾病相关。代谢综合征是多种危险因素的综合，包括葡萄糖耐量降低，高密度脂蛋白增加，腹部肥胖和高血压。这项研究的目的是评估苏伊士运河地区的埃及妇女中miRNA-146a rs2910164与代谢综合征及其组成特征的关系。该研究包括100名健康女性受试者和100名代谢综合征患者。使用限制酶Hpy188I，通过聚合酶链反应-限制性片段长度多态性技术，确定代谢综合征的组成特征，并评估多态性的基因型。罕见的C等位基因在代谢综合征患者中的发生频率显着更高（P = 0.013）。杂合子GC和罕见的CC基因型显示出体重指数，腰围，甘油三酸酯，总胆固醇，低密度脂蛋白，收缩压和舒张压显着增加。 GC基因型与较高的空腹血糖，空腹血清胰岛素和胰岛素抵抗有关。与GG基因型携带者相比，CC基因型携带者具有显着更低的HDL。总之，在研究人群中，miRNA-146a rs2910164的C等位基因与代谢综合征及其表型的敏感性增加呈正相关。

BACKGROUND & AIMS: BACKGROUND:Several studies have reported the role of the miR-146a rs2910164 G > C polymorphism as a susceptibility factor for several digestive cancers. However, the results have been controversial. Therefore, we conducted the present meta-analysis to obtain the most reliable estimate of the association. METHODS:PubMed, Embase and Web of Science databases were searched. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were extracted and pooled to assess the strength of the association between miR-146a rs2910164 G > C polymorphism and digestive cancer risk. A total of four eligible studies including 3,447 cases and 5,041 controls based on the search criteria were included. RESULTS:We observed that miR-146a rs2910164 G > C polymorphism was not significantly correlated with digestive cancer risks when all studies were pooled into the meta-analysis. While we found that miR-146a rs2910164 polymorphism was not associated with gastric cancer, it was significantly linked with hepatocellular cancer risk (the homozygote codominant model: OR = 1.40, 95% CI = 1.04-1.87). In the stratified analysis by ethnicity, significant associations were observed in Chinese population for the allele contrast model (OR = 1.25; 95% CI = 1.12-1.38), for the homozygote codominant model (OR = 1.62; 95% CI = 1.28-2.04), and for the recessive model (OR = 1.38; 95% CI = 1.16-1.64). However, studies with Asian groups presented no significant association for all genetic models. CONCLUSIONS:This meta-analysis suggests that the miR-146a rs2910164 G > C polymorphism is a low-penetrant risk factor for digestive cancers in Chinese.

背景与目标： 背景：多项研究报告了miR-146a rs2910164 G> C多态性作为几种消化道癌症的易感因素的作用。但是，结果一直存在争议。因此，我们进行了本次荟萃分析，以获得最可靠的关联估计。
方法：检索PubMed，Embase和Web of Science数据库。提取具有95％置信区间（CI）的原始比值比（OR）并合并，以评估miR-146a rs2910164 G> C多态性与消化道癌症风险之间的关联强度。根据搜索标准，总共纳入了四项合格研究，包括3447例病例和5,041例对照。
结果：我们观察到，将所有研究纳入荟萃分析后，miR-146a rs2910164 G> C多态性与消化道癌症风险没有显着相关性。尽管我们发现miR-146a rs2910164多态性与胃癌无关，但它与肝细胞癌风险显着相关（纯合子显性模型：OR = 1.40，95％CI = 1.04-1.87）。在按族裔进行的分层分析中，在中国人群中，等位基因对比模型（OR = 1.25； 95％CI = 1.12-1.38），纯合子显性模型（OR = 1.62； 95％CI = 1.28-2.04）之间存在显着关联。 ），以及隐性模型（OR = 1.38; 95％CI = 1.16-1.64）。但是，与亚洲人群的研究表明，所有遗传模型之间均无显着关联。
结论：这项荟萃分析表明，miR-146a rs2910164 G> C多态性是中国消化道癌的低渗透危险因素。

BACKGROUND & AIMS: BACKGROUND:South African (SA) Black women have a high prevalence of preeclampsia and HIV, both conditions associated with increased inflammation. miR-146a is an inflammatory-associated miR and a common single nucleotide polymorphism (rs2910164) has been associated with several disease conditions. To date, this SNP has not been investigated in SA Black women. We therefore aimed to investigate the miR-146a G > C SNP in SA Blacks with preeclampsia, and further examine possible association among preeclamptic (PE) women with HIV infection on HAART. METHODS:This hospital-based, case-control study included 95 normotensive and 98 PE Black SA women (aged 16-46 years old). Patients and controls were genotyped by PCR-RFLP. Using a Cytometric Bead Array assay, serum cytokine levels (including Th1- and Th2-related cytokines) were determined in 4 groups of pregnant women, viz: normotensive, HIV infected, PE + HIV infected, and PE women. RESULTS:There was no significant association between the miR-146a polymorphism and PE susceptibility in our data. However, in the subgroup analyses, the variant genotypes (GC/CC) were significantly associated with lower severe PE risk (p = 0.0497), more especially in the presence of HIV and HAART (p = 0.017). In the normotensive group, the variant genotypes were associated with lower IL-2 in both the total normotensive group (269 ± 1.26 (36) vs 273 ± 1.31 (23); p = 0.035) and the PE HIV+ sub-group 265 ± 1.54 (19) vs 271 ± 1.38 (11); p = 0.008). CONCLUSIONS:Our study suggests that miR-146a rs2910164 polymorphism might not be associated with PE susceptibility, cytokines or related features. However, the miR-146a GC/CC genotype might reduce susceptibility to severe PE, which might be further influenced by the presence of co-morbid HIV infection among pregnant women on HAART. This variant genotype may also be associated with reduced circulating IL-2 levels and thus reduced pro-inflammatory response in normotensive women, which may be further influenced by the presence of HIV infection and HAART.

背景与目标： 背景：南非黑人妇女患有先兆子痫和艾滋病毒，这两种情况都与炎症增加有关。 miR-146a是一种与炎症相关的miR，常见的单核苷酸多态性（rs2910164）与多种疾病相关。迄今为止，尚未在SA黑人妇女中对该SNP进行过调查。因此，我们旨在调查子痫前期黑人中的miR-146a G> C SNP，并进一步检查子痫前期（PE）妇女在HAART上感染HIV的可能关联。
方法：这项基于医院的病例对照研究包括95名血压正常和98名PE Black SA妇女（年龄16-46岁）。通过PCR-RFLP对患者和对照进行基因分型。使用细胞计数珠阵列测定法，确定了4组孕妇的血清细胞因子水平（包括Th1和Th2相关的细胞因子），即血压正常，HIV感染，PE 3 + HIV感染和PE妇女。
结果：在我们的数据中，miR-146a多态性与PE易感性之间没有显着关联。然而，在亚组分析中，变异基因型（GC / CC）与较低的严重PE风险显着相关（p = 0.0497），尤其是在存在HIV和HAART的情况下（p = 0.017）。在血压正常组中，总血压正常组中的变异基因型与较低的IL-2相关（269±±1.26（36）vs 273±±1.31（23）； p = 0.035）和PE HIV亚组265±1.54 （19）vs 271±1.38（11）; p = 0.008）。
结论：我们的研究表明，miR-146a rs2910164多态性可能与PE易感性，细胞因子或相关特征无关。但是，miR-146a GC / CC基因型可能会降低对严重PE的易感性，这可能进一步受到HAART孕妇中合并感染HIV的感染的影响。这种变异的基因型也可能与循环中的IL-2水平降低有关，从而降低了血压正常女性的促炎反应，这可能进一步受到HIV感染和HAART的影响。

BACKGROUND & AIMS: :Background. Single nucleotide polymorphisms (SNPs) in genes encoding microRNAs may play important role in the development of gastric cancer. It has been reported that common SNPs rs2910164 in miR-146a and rs11614913 in miR-196a2 are associated with susceptibility to gastric cancer. The published results remain inconclusive or even controversial. A meta-analysis was conducted to quantitatively assess potential association between the two common SNPs and gastric cancer risk. Methods. A comprehensive literature search was performed in multiple internet-based electronic databases. Data from 12 eligible studies were extracted to estimate pooled odds ratios (ORs) and 95% confidence intervals (95% CI). Results. C allele of rs2910164 is associated with reduced gastric cancer risk in heterozygote model and dominant model whereas rs11614913 indicates no significant association. Subgroup analysis demonstrates that C allele of rs2910164 and rs11614913 may decrease susceptibility to diffuse type gastric cancer in dominant model and recessive model, respectively, while rs11614913 increased intestinal type gastric cancer in dominant model. Conclusion. SNPs rs2910164 and rs11614913 might have effect on gastric cancer risk in certain genetic models and specific types of cancer. Further well-designed studies should be considered to validate the potential effect.

背景与目标： ：背景。编码microRNA的基因中的单核苷酸多态性（SNP）可能在胃癌的发生中起重要作用。据报道，miR-146a中常见的SNP rs2910164和miR-196a2中常见的rs11614913与胃癌的易感性有关。发表的结果仍然没有定论，甚至是有争议的。进行荟萃分析以定量评估两种常见SNP与胃癌风险之间的潜在关联。方法。在多个基于互联网的电子数据库中进行了全面的文献搜索。提取了来自12项合格研究的数据，以估计合并的优势比（OR）和95％的置信区间（95％CI）。结果。 rs2910164的C等位基因与杂合子模型和显性模型中降低的胃癌风险相关，而rs11614913表明无显着相关性。亚组分析表明，rs2910164和rs11614913的C等位基因可能在显性模型和隐性模型中分别降低对弥漫型胃癌的易感性，而rs11614913在显性模型中增加肠型胃癌的易感性。结论。在某些遗传模型和特定类型的癌症中，SNP rs2910164和rs11614913可能对胃癌风险有影响。应该考虑进行进一步设计良好的研究，以验证潜在的效果。

BACKGROUND & AIMS: :We conducted a case-control study investigating the association between the single-nucleotide polymorphism rs2910164 in microRNA (miR)-146a and the risk and prognosis of stroke. We recruited a total of 1139 ischemic stroke patients and 1585 sex- and age-matched control subjects. After a median follow-up period of 4.5 years, 1071 of these ischemic stroke patients were then recruited for a prospective study. Our study revealed that rs2910164 was not associated with ischemic stroke incidence (odds ratio = 1.00; 95% confidence interval (CI) = 0.80-1.24; p = 0.985) by multivariate logistic regression. Meta-analysis of our case-control study and three others on Asian populations also suggested that there was no relationship between rs2910164 and ischemic stroke incidence. The significance of differences in long-term outcomes was examined by the log-rank test of the respective comparison groups. The prospective study showed that rs2910164 led to a 1.56-fold increased risk of stroke recurrence (hazard ratio (HR) = 1.56; 95% CI = 1.10-2.20; p = 0.013) and a 2.13-fold increased risk of death caused by cardiovascular disease or stroke (Csdeath) (HR = 2.13; 95% CI = 1.31-3.46; p = 0.002). The independent association of rs2910164 with stroke prognosis was evaluated using Cox regression models. Therefore, rs2910164 appears to be a strong predictor of stroke prognosis but not of stroke incidence in Asian populations.

背景与目标： ：我们进行了一项病例对照研究，研究了microRNA（miR）-146a中的单核苷酸多态性rs2910164与卒中的风险和预后之间的关系。我们共招募了1139名缺血性中风患者和1585名性别和年龄匹配的对照受试者。在中位随访期为4.5年之后，随后招募了这些缺血性卒中患者中的1071例进行前瞻性研究。我们的研究表明，通过多元逻辑回归分析，rs2910164与缺血性卒中发生率无关（几率= 1.00； 95％置信区间（CI）= 0.80-1.24； p = 0.985）。对我们的病例对照研究和其他三项关于亚洲人群的荟萃分析也表明，rs2910164与缺血性中风发生率之间没有关系。长期结果差异的显着性通过各个比较组的对数秩检验进行检验。前瞻性研究表明，rs2910164导致中风复发的风险增加了1.56倍（危险比（HR）= 1.56； 95％CI = 1.10-2.20； p = 0.013），心血管疾病导致的死亡风险增加了2.13倍。疾病或中风（Csdeath）（HR = 2.13; 95％CI = 1.31-3.46; p = 0.002）。使用Cox回归模型评估rs2910164与中风预后的独立关联。因此，在亚洲人群中，rs2910164似乎是中风预后的有力预测指标，而不是中风发生率的强预测指标。

BACKGROUND & AIMS: BACKGROUND:Evidence has shown that single nucleotide polymorphism located in pre-miRNA or mature microRNA may modify various biological processes and affect the processing of carcinogenesis. Published results about the association between miR-146a rs2910164 G/C polymorphism and human gastric cancer susceptibility are inconclusive. The aim of this study was to acquire a more precise effect of the association between the miR-146a rs2910164 polymorphism and gastric risk by meta-analysis. METHODS:Eligible genetic association studies were searched from PubMed, Web of Knowledge and Chinese Biomedicine Database on human subject. Quantitative data synthesis was conducted for the associations of miR-146a rs2910164 G/C polymorphism with susceptibility to gastric cancer. RESULTS:Nine eligible studies that included a total of 3,885 gastric cancer patients and 5,396 controls were identified in the present meta-analysis. The overall OR indicated a potential association between rs2910164 polymorphism and GC but the effect was not statistically significant (GG vs. CG/CC:OR = 1.076, 95% CI 0.925-1.251, P = 0.342). When stratifying for population, the result showed that miR-146a rs2910164 GG genotype was associated with increased gastric cancer risk among Chinese in recessive model (GG vs. CG/CC:OR = 1.171, 95% CI 1.050-1.306, P = 0.005). Besides, no significant difference was found in gender, smoking, location, metastasis of lymph node and Laurèn's classification. CONCLUSIONS:The present meta-analysis suggests an increased risk between miR-146a rs2910164 GG genotype and gastric cancer susceptibility in Chinese based on published literatures.

背景与目标： 背景：证据表明，位于pre-miRNA或成熟microRNA中的单核苷酸多态性可能会改变各种生物学过程并影响致癌过程。关于miR-146a rs2910164 G / C多态性与人胃癌易感性之间关系的已发表结果尚无定论。这项研究的目的是通过荟萃分析获得miR-146a rs2910164多态性与胃癌风险之间关联的更精确效果。
方法：从PubMed，Web of Knowledge和中国生物医学数据库中检索有关人类受试者的合格遗传关联研究。进行了miR-146a rs2910164 G / C多态性与胃癌易感性相关性的定量数据综合。
结果：本荟萃分析共鉴定出9项合格研究，共3885例胃癌患者和5396例对照患者。总体OR表示rs2910164多态性与GC之间存在潜在的关联，但效果无统计学意义（GG vs.
CG / CC：OR = 1.076，95％CI 0.925-1.251，P = 0.342）。当按人群分层时，结果显示，在隐性模型中，miR-146a rs2910164 GG基因型与中国胃癌风险增加相关（GG vs.
CG / CC：OR = 1.171，95％CI 1.050-1.306，P = 0.005）。此外，在性别，吸烟，淋巴结转移，淋巴结转移和劳伦分类方面无显着差异。
结论：目前的荟萃分析表明，根据已发表的文献，中国人miR-146a rs2910164 GG基因型与胃癌易感性之间的风险增加。