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。

BACKGROUND & AIMS: :The rs2910164:G>C SNP is located in the gene for miR-146a, a microRNA that binds the 3' UTR of the BRCA1 transcript. Preliminary data based on the analysis of a small number of cases suggested that this single nucleotide polymorphism (SNP) might be associated with the age of onset of familial breast and ovarian cancer. This effect was not confirmed on a large series of familial breast cancer cases negative for a BRCA1 or BRCA2 mutation. We show here a lack of association of the rs2910164:G>C SNP with breast cancer risk in a series of 1,166 BRCA1 and 560 BRCA2 mutation carriers. In conclusion, the polymorphism in the miR-146a gene is unlikely to be of substantial significance regarding breast cancer risk.

背景与目标： ：rs2910164：G> C SNP位于miR-146a的基因中，miR-146a是与BRCA1转录物的3'UTR结合的微RNA。根据对少数病例的分析得出的初步数据表明，这种单核苷酸多态性（SNP）可能与家族性乳腺癌和卵巢癌的发病年龄有关。在一系列对BRCA1或BRCA2突变呈阴性的家族性乳腺癌病例中，尚未确认这种效果。我们在此处显示了在一系列1,166个BRCA1和560个BRCA2突变携带者中，rs2910164：G> C SNP与乳腺癌风险之间缺乏关联。总之，就乳腺癌风险而言，miR-146a基因的多态性不太可能具有实质性意义。

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

背景与目标： ：子痫前症（PE）是一种妊娠疾病，遗传和表观遗传学改变可能会影响其发病机理。一些证据表明，miRNA在胎盘中的表达改变并发PE。收集了219名PE和242名血压正常孕妇的血液样本以及111名PE和119名血压正常女性的胎盘组织样本。使用PCR-RFLP方法对血液样本和胎盘中的MiR-146a和miR-149多态性进行基因分型。 PE和对照组之间，母亲miR-146a rs2910164 GC和CC基因型的频率无差异。然而，miR-146a rs2910164 G / C多态性与显性（OR 1.5，95％CI 1-2.1； P = 0.04）和等位基因（OR 1.4，95％CI 1-1.9； P = 0.04），但不是隐性模型。此外，母亲GC和CC基因型与严重PE风险增加1.9和3.4倍相关（OR 1.9，95％CI 1.1-3.2； P = 0.02； OR 3.4，95％CI 1.3-9; P = 0.01和0.01）和miR-146a rs2910164多态性可能在显性和隐性模型中增加发生严重PE的风险（OR 2.1，95％CI 1.3-3.4; P = 0.004和OR 2.6，95％CI 1-6.7; P = 0.04） 。胎盘miR-146a rs2910164多态性与显性（OR 1.8，95％CI 1.1-3; P = 0.03）和等位基因模型（OR 1.7，95％CI 1.1-2.5; P = 0.02）的PE易感性有关。两组之间的母亲和胎盘miR-149 rs2292832基因型的频率没有差异，并且这些基因型与PE或严重的PE风险无关。总之，根据逻辑回归分析，母亲/胎盘miR-146a rs2910164 G / C多态性与PE和/或严重PE风险相关。

BACKGROUND & AIMS: :MicroRNAs (miRNAs) are a group of non-coding RNAs that play a role in gene regulation. Due to their possible functional importance, genetic variants within miRNA genes have been recognized as candidate biomarkers. Single-nucleotide polymorphisms (SNPs) in miRNA genes can be related to the risk of different autoimmune diseases. Some of these SNPs are rs2910164 in the miR-146a and rs1044165 in the miR-223. The aim of this study was to investigate the relationship between these polymorphisms and the risk of multiple sclerosis (MS) in an Iranian population. In this case-control study, 261 patients with MS and 250 healthy controls that matched by age and geographical region were enrolled. After sampling and genomic DNA extraction, genotyping was determined by PCR-restriction fragment length polymorphism. Allelic and genotypic associations between the SNPs and MS were evaluated by the data analysis conducted by SPSS V.20. The frequencies of rs2910164 and rs1044165 SNPs were significantly different between the patients with MS and healthy controls. C and T alleles in the variants rs2910164 and rs1044165, respectively, are associated with increased risk of MS. Such association was obtained in codominant, dominant, and overdominant models for both variants (OR ~3 and OR ~1.5, respectively). Furthermore, this study determined that the C and T alleles of rs2910164 and rs1044165 are risk factors for MS in the Iranian population.

背景与目标： ：MicroRNA（miRNA）是在基因调控中起作用的一组非编码RNA。由于其可能的功能重要性，miRNA基因内的遗传变异已被视为候选生物标记。 miRNA基因中的单核苷酸多态性（SNP）可能与各种自身免疫性疾病的风险有关。这些SNP中的一些是miR-146a中的rs2910164和miR-223中的rs1044165。这项研究的目的是调查伊朗人群中这些多态性与多发性硬化症（MS）风险之间的关系。在该病例对照研究中，纳入了261例MS患者和250例按年龄和地理区域匹配的健康对照。采样和基因组DNA提取后，通过PCR限制性片段长度多态性确定基因分型。通过SPSS V.20进行的数据分析评估了SNP与MS之间的等位基因和基因型关联。患有MS的患者和健康对照组之间的rs2910164和rs1044165 SNP的频率显着不同。 rs2910164和rs1044165变体中的C和T等位基因分别与MS风险增加相关。在两个变体的共显性，显性和显性模型中分别获得了这种关联（分别为OR〜3和OR〜1.5）。此外，这项研究确定rs2910164和rs1044165的C和T等位基因是伊朗人群MS的危险因素。

BACKGROUND & AIMS: OBJECTIVE:Today, many single nucleotide polymorphisms in microRNA genes are known to alter the microRNA expression levels or processing causing susceptibility of several human diseases. The present study aimed to investigate the association of microRNA-146a (rs2910164) and microRNA-222 (rs2858060) polymorphisms with susceptibility to polycystic ovary syndrome (PCOS) in an Iranian population. MATERIALS AND METHODS:This case-control study was performed on 205 patients with PCOS and 205 normal women as the control group. After DNA extraction, Tetra-amplification refractory mutation system polymerase chain reaction (T-ARMS-PCR) was used to detect the polymorphisms. The association between genotypes and the risk of PCOS was examined by odds ratios (OR) and 95% of confidence intervals (CIs). RESULTS:Our results showed that there are significant differences in CG genotype frequencies between case and control groups regarding miR-146a rs2910164 polymorphism (OR = 2.03, CI = 1.3-3, P = 0.001). In a dominant model for the C allele, CC + CG genotypes were associated with PCOS risk (OR = 2, 95% CI = 1.3-2.9, P = 0.001) and the C allele increased the risk of PCOS (OR = 1.6, 95% CI = 1.1-2.1, P = 0.004). Furthermore, a positive association was observed between miR-222 CG genotype and the risk of PCOS (OR = 2.2, 95% CI = 1.1-4.1, P = 0.02). These results were evident after adjustment for age and body mass index. CONCLUSION:The present results suggest that the miR-146a rs2910164 and miR-222 rs2858060 polymorphisms are associated with an increased risk of PCOS. Therefore, both polymorphisms could play an important role as a genetic risk factor for development of PCOS in the Iranian population.

背景与目标： 目的：今天，已知许多微小RNA基因中的单核苷酸多态性会改变微小RNA的表达水平或加工过程，从而导致多种人类疾病的易感性。本研究旨在调查伊朗人群中microRNA-146a（rs2910164）和microRNA-222（rs2858060）多态性与多囊卵巢综合征（PCOS）易感性的关系。
材料与方法：本病例对照研究以205例PCOS患者和205例正常女性为对照组。 DNA提取后，四扩增难治性突变系统聚合酶链反应（T-ARMS-PCR）用于检测多态性。通过比值比（OR）和95％的置信区间（CIs）检查基因型与PCOS风险之间的关联。
结果：我们的结果表明，案例组和对照组之间的miR-146a rs2910164多态性在CG基因型频率上存在显着差异（OR = 2.03，CI = 1.3-3，P = 0.001）。在C等位基因的显性模型中，CC CG基因型与PCOS风险相关（OR = 2，95％CI = 1.3-2.9，P = 0.001），C等位基因增加了PCOS的风险（OR = 1.6，95％ CI = 1.1-2.1，P = 0.004）。此外，观察到miR-222 CG基因型与PCOS风险呈正相关（OR = 2.2，95％CI = 1.1-4.1，P = 0.02）。调整年龄和体重指数后，这些结果显而易见。
结论：目前的结果表明，miR-146a rs2910164和miR-222 rs2858060多态性与PCOS风险增加有关。因此，两种多态性都可能作为伊朗人群中PCOS发生的遗传危险因素而发挥重要作用。

BACKGROUND & AIMS: BACKGROUND/AIMS:MicroRNAs (miRNAs) are a class of small non-coding RNA molecules which play a significant role in transcriptional and translational regulation. Published data on the association between the miRNA SNPs and prostate cancer (PCa) risk are somewhat inconclusive. METHODS:We performed a meta-analysis of all available studies including 2,227 patients and 2,331 control subjects to evaluate the impact of three common genetic variants of microRNAs in prostate cancer risk. Odds ratios (ORs) with 95% confidence intervals (CIs) were utilized to investigate the strength of the association. RESULTS:For miR-499 polymorphism, a significant association was observed between the rs3746444 A>G polymorphism and PCa risk in heterozygote comparison and dominant genetic model, in particular in Asian population subgroup. For miR-146a polymorphism, the rs2910164 CC genotype was associated with decreased PCa risk in Asian population in homozygote comparison. In addition, rs2910164 CC genotype had a weekly higher percentage value in subgroup of Gleason score < 7. Similar results were also indicated in localized prostate cancer in subgroup analysis by tumor stage. For miR-196a2 polymorphism, no association was observed between this variant and PCa risk in the overall group. However, in stratified analysis by ethnicity, we found that rs11614913 T allele was a risk factor for Asian PCa patients. CONCLUSIONS:Polymorphisms of miR-196a2 rs11614913, miR-146a rs2910164, and miR-499 rs3746444 may contribute to the risk for developing prostate cancer in Asian descendants. Moreover, miR-146a rs2910164 polymorphism was related to PCa prognosis.

背景与目标： 背景/目的：微小RNA（miRNA）是一类小的非编码RNA分子，在转录和翻译调控中起着重要作用。关于miRNA SNP与前列腺癌（PCa）风险之间关系的已发表数据尚无定论。
方法：我们对包括2,227例患者和2,331例对照受试者在内的所有可用研究进行了荟萃分析，以评估microRNA的三种常见遗传变异对前列腺癌风险的影响。具有95％置信区间（CI）的几率（OR）用于研究关联的强度。
结果：对于miR-499多态性，在杂合子比较和优势遗传模型中，尤其是亚洲人群中，观察到rs3746444 A> G多态性与PCa风险之间存在显着关联。对于miR-146a多态性，纯合子比较显示，rs2910164 CC基因型与亚洲人群PCa风险降低相关。此外，rs2910164 CC基因型在Gleason评分<7的亚组中每周有更高的百分比值。在按肿瘤分期进行的亚组分析中，局部前列腺癌也显示了相似的结果。对于miR-196a2多态性，在整个组中未观察到此变异与PCa风险之间的关联。但是，在按种族进行的分层分析中，我们发现rs11614913 T等位基因是亚洲PCa患者的危险因素。
结论：miR-196a2 rs11614913，miR-146a rs2910164和miR-499 rs3746444的多态性可能会导致亚洲后裔患上前列腺癌的风险。此外，miR-146a rs2910164多态性与PCa的预后有关。

BACKGROUND & AIMS: BACKGROUND/AIMS:MicroRNAs post-transcriptionally regulate the expression of their target genes and their function in a wide range of physiological pathways. Aberrant expression of microRNAs has been implicated in the development of human malignant tumors. Recent reports showed that two single nucleotide polymorphisms (SNPs), miR-146a rs2910164 and miR-196a2 rs11614913, are associated with increased risk of human gastric cancer. Nevertheless, results from the published reports are still inconsistent and inconclusive. Thus, we conducted this meta-analysis study to further evaluate the effects of these two SNPs on susceptibility to human gastric cancer. MATERIALS AND METHODS:Using specific inclusion and exclusion criteria, we extracted data from selected studies that were identified from electronic databases, such as PubMed, Embase, and Wanfang. Odds ratio (ORs) and 95% CIs were then obtained to determine the impact of the two SNPs on susceptibility to human gastric cancer using the statistical software Stata. RESULTS:We identified six studies on rs2910164 and five reports regarding rs11614913 for our meta-analysis. Our data demonstrated that the two SNPs rs2910164 and rs11614913 do not produce any effects on the risk of human gastric cancer under all genetic models. CONCLUSION:There is no significant association between rs2910164 and rs11614913 and the risk of human gastric cancer. However, future studies with large and homogeneous population of patients with gastric cancer and well-matched controls are needed to validate these findings.

背景与目标： 背景/目的：MicroRNA在多种生理途径中转录后调控其靶基因的表达及其功能。 microRNA的异常表达与人类恶性肿瘤的发展有关。最近的报告显示，两个单核苷酸多态性（SNP）miR-146a rs2910164和miR-196a2 rs11614913与人类胃癌的风险增加相关。但是，已发布报告的结果仍然不一致且无定论。因此，我们进行了这项荟萃分析研究，以进一步评估这两个SNP对人胃癌易感性的影响。
材料与方法：使用特定的纳入和排除标准，我们从选定的研究中提取数据，这些研究是从电子数据库（例如PubMed，Embase和Wanfang）中鉴定出来的。然后使用统计软件Stata获得比值比（OR）和95％CI，以确定这两个SNP对人胃癌易感性的影响。
结果：我们对rs2910164进行了六项研究，并针对rs11614913进行了五篇报告，用于我们的荟萃分析。我们的数据表明，在所有遗传模型下，两个SNP rs2910164和rs11614913均不会对人胃癌的风险产生任何影响。
结论：rs2910164和rs11614913与人类胃癌的风险之间没有显着相关性。但是，需要对大量且均质的胃癌患者和匹配良好的对照进行进一步的研究，以验证这些发现。

BACKGROUND & AIMS: BACKGROUND:Exposure to ubiquitous polycyclic aromatic hydrocarbons (PAHs) has been associated with decreased heart rate variability (HRV). Evidence accumulates that microRNAs (miRNAs) might be the intermediate factors between environmental exposures and their adverse health effects. Single nucleotide polymorphisms (SNPs) in miRNA genes may affect phenotypes and disease morbidity. OBJECTIVE:We sought to investigate the influences of four well-studied SNPs in miRNA genes (rs2910164, rs11614913, rs2292832, and rs3746444) on HRV, and their modifying effects on the associations between PAH exposure and HRV. METHODS:We measured the concentrations of ten urinary monohydroxy PAHs (OH-PAHs), seven HRV parameters, and genotypes of these four SNPs in 1222 coke oven workers. RESULTS:There were significant differences among different rs2910164 genotype carriers in terms of all seven HRV indices: workers with rs2910164 CC genotype had significant lower HRV than those with GG or GC genotype (P<0.05). The number of rs2910164 C allele was negatively associated with HRV indices in the high PAH exposure group (β<0, P<0.05), and the association between rs2910164 and high-frequency (HF) power was significantly stronger in high exposure group (Pinteraction=0.042). Interestingly, the negative associations between the sum of 10 OH-PAHs and HRV (β<0, P<0.05) were significantly or marginally significantly stronger in workers with rs2910164 CC genotype (Pinteraction≤0.050). CONCLUSIONS:Coke oven workers with miR-146a rs2910164 CC genotype may be more susceptible to decreased HRV. The modifying effect of rs2910164 on the PAHs-HRV associations suggested miR-146a may mediate the effects of PAH exposure on HRV.

背景与目标： 背景：暴露于普遍存在的多环芳烃（PAHs）与降低心率变异性（HRV）有关。有证据表明，微小RNA（miRNA）可能是环境暴露与其不良健康影响之间的中间因素。 miRNA基因中的单核苷酸多态性（SNP）可能影响表型和疾病发病率。
目的：我们试图研究miRNA基因（rs2910164，rs11614913，rs2292832和rs3746444）中四个经过充分研究的SNP对HRV的影响，以及它们对PAH暴露与HRV之间关联的修饰作用。
方法：我们测量了1222名炼焦炉工人中十种尿一羟基PAHs（OH-PAHs）的浓度，七个HRV参数以及这四个SNP的基因型。
结果：在所有七个HRV指数方面，不同rs2910164基因型携带者之间存在显着差异：rs2910164 CC基因型的工人的HRV显着低于GG和GC基因型的工人（P <0.05）。高PAH暴露组中rs2910164 C等位基因的数目与HRV指数呈负相关（β<0，P <0.05），高暴露组中rs2910164与高频（HF）功率之间的相关性明显更强（交互作用） = 0.042）。有趣的是，rs2910164 CC基因型（交互作用≤0.050）的工人中，10个OH-PAHs的总和与HRV之间的负相关性（β<0，P <0.05）显着或略有显着增强。
结论：miR-146a rs2910164 CC基因型的炼焦炉工人可能更容易降低HRV。 rs2910164对PAHs-HRV关联的修饰作用表明，miR-146a可能介导PAH暴露对HRV的影响。