Pre-miR-146a基因rs2910164位点单核苷酸基因多态性及miR-146a表达与类风湿关节炎相关性研究

目的 探讨pre-miR-146a基因rs2910164位点单核苷酸基因多态性及miR-146a表达与类风湿关节炎相关性.方法 采用聚合酶链反应-连接酶检测反应检测123例类风湿关节炎(RA)患者和220例健康对照者pre-miR-146a rs2910164位点基因多态性,应用实时荧光定量聚合酶链反应检测68例RA患者、10例骨关节炎(OA)患者及20例健康对照外周血单个核细胞中miR-146a的表达水平,并选取10例RA疾病活动患者行激素加免疫抑制剂正规治疗3个月后miR-146a表达水平的测定.收集并计算RA患者临床参数:发病年龄、性别、类风湿因子(RF)和抗环瓜氨酸肽(抗-CCP)抗体、RA疾病活动(DAS28≥3.2)、骨破坏(X＞Ⅰ期).统计学处理采用X2检验、方差分析、t检验和Pearson相关分析.结果 RA组pre-miR-146a rs2910164位点的基因型频率和等位基因频率与健康对照组比较,差异无统计学意义(P均＞0.05).RA患者pre-miR-146ars2910164位点基因型与发病年龄、性别、RF和抗-CCP抗体阳性率、RA疾病活动、骨破坏阳性率及miR-146a表达量均无相关性(P均＞0.05).RA患者组miR-146a的表达量高于健康对照组和OA组(P均＜0.01),后两组miR-146a的表达量无统计学差异(P＞0.05).RA疾病活动组miR-146a表达高于非活动组和对照组(P均＜0.01),后两组miR-146a的表达量无统计学差异(P＞0.05).RA疾病活动患者治疗后miR-146a表达下降(P＜0.05),DAS28评分降低(P＜0.01).RA患者组miR-146a的表达与红细胞沉降率(ESR,即血沉)、C反应蛋白(CRP)及DAS28评分之间呈正相关(P均＜0.01),与RF、抗-CCP抗体滴度无相关性(P均＞0.05).结论 我国汉族人群中,pre-miR-146a rs2910164位点多态性与RA的易感性、临床参数及miR-146a的表达无相关性,RA患者外周血单个核细胞miR-146a表达上调,其表达水平与RA病情活动有关,miR-146a的检测可能是RA病情活动的一个有用的判断指标.     

miR-146a单核苷酸多态性rs2910164与恩施地区人群痛风及高尿酸血症的相关性研究

为探讨miR-146a基因单核苷酸rs2910164位点多态性与恩施地区痛风及高尿酸血症的相关性,分别收集健康对照者296例、原发性痛风患者159例和高尿酸血症患者197例.采用高单核苷酸多态性(Hi-single nucleotide polymorphism,Hi-SNP)结合多重PCR和高通量测序技术检测miR-...     

miR-146a基因rs2910164 G/C多态性与miR-146a异常表达与胃癌风险相关性的研究

目的:探讨miR-146a基因单核苷酸多态位点rs2910164 G/C是否影响miR-146a的表达并改变其对胃癌的易感性。方法:选取53例胃癌患者和6株胃癌细胞株(AGS、BGC-823、HGC27、MKN-28、MKN-45和SGC-7901),采用Taqman定量PCR检测miR-146a的表达,构建miR-1...     

microRNA-146a与2型糖尿病的相关性研究进展

2型糖尿病是由遗传因素和环境因素共同导致的复杂疾病,胰岛素抵抗和胰岛β细胞功能障碍是其主要的发病机制.miRNAs是一类内源性非编码小RNA,通过调控各种基因的表达广泛参与细胞增殖、分化、凋亡、代谢等生物过程.近年研究发现,miRNA-146a与糖尿病、心血管疾病、自身免疫性疾病以及肿瘤等疾病密切相关,但miRNA-146a在2型糖尿病中的作用机制尚不清楚,还需进一步明确miRNA-146a对其的作用机制.该文就miRNA-146a与2型糖尿病及其并发症之间的相关性作一综述.     

FTO rs8050136多态性与黑龙江地区汉族人群2型糖尿病的相关性

目的探讨FTO基因rs8050136单核苷酸多态性与2型糖尿病（T2DM）的相关性。方法采用病例对照研究：病例组为500例,对照组为500例。利用SNa Pshot方法检测基因型。研究FTO基因rs8050136等位基因、基因型和显性模型与T2DM的关系。结果 FTO基因SNP rs8050136等位基因A与C相比,在T2DM组和对照组间的分布频率有统计学意义（P〈0.05,OR：1.28,95%CI：1.12~1.54）;与CC基因型相比,CA基因型和显性模型CA＋AA在两组间的比较有显著差异（P〈0.05,OR：1.25,95%CI：1.03~1.59;P〈0.05,OR：1.29,95%CI：1.13~1.47）。结论 FTO基因SNP rs8050136增加我省人群患T2DM的风险。     

中国人膜联蛋白A1基因单核苷酸多态性及其与2型糖尿病的相关性

目的　筛查上海地区汉族人群中膜联蛋白 A1(annexin A1,ANXA1)基因的单核苷酸多态性 (single nucleotide polymorphisms,SNPs) ,并通过关联分析研究其与 2型糖尿病的相关性。方法　选取2 4例 2型糖尿病患者的 DNA样本 ,采用直接测序法对 ANXA1基因的启动子区、全部外显子及其临近内含子区作 SNPs筛查 ,并在其余的 171例 2型糖尿病和 189名正常对照间作进一步的基因分型。结果ANXA1基因测序长度 6 798bp,共检出 7个 SNPs,其中启动子区 2个 (- 7974 C>T,- 70 4 0 G>T) ,内含子区 3个 ( 90 5 9A>G, 92 0 4 C>T, 10 4 86 A>G) ,5′-非翻译区 1个 (- 6 6 14 A>G) ,编码区 1个( 1784 A>G)。进一步的基因分型后显示这些 SNPs的等位基因频率在 2型糖尿病和正常对照组之间差异无显著性 (P>0 .0 5 )。结论　ANXA1基因多态性与上海地区汉族人群中 2型糖尿病无显著相关性。     

MTNR1B基因多态性与2型糖尿病

2型糖尿病是一种与多基因、多因素相关联的具有明显遗传异质性的疾病.全基因组关联分析显示MTNR1B基因变异与胰岛素分泌、葡萄糖水平以及2型糖尿病发病有显著相关性.MTNR1B基因是2型糖尿病重要的易感基因之一,其变异可能通过减少β细胞胰岛素分泌,从而增加2型糖尿病的易感性.     

中国广西人群miR-146a、miR-149 基因遗传多态性的研究

目的：研究广西人群miR-146a C>G (rs2910164）、miR-149 T>C（rs2292832）等位基因及基因型频率分布,分析其与不同民族种族间的差异性。方法：采用单碱基延伸技术和DNA测序技术对303例广西人群中miR-146a C>G和miR-149 T>C基因单核苷酸多态性(SNP)位点进行分型检测,并与人类基因组计划 (Hapmap) 数据库中公布的非洲人、欧洲人、日本人和中国北京人群的SNP分型数据比较。结果：miR-146a C>G、miR-149 T>C等位基因和基因型频率在广西男女人群之间分布均无差异性（P均>0.05）。广西人群miR-146a C>G和miR-149 T>C基因型及等位基因频率与非洲人、欧洲人、中国北京人比较有统计学意义（P均<0.05）。结论：广西人群miR-146a C>G和miR-149 T>C存在基因多态性,与其他种族人群比较有差异性,这种差异性对人类遗传病的研究可能会起到重要作用。     

磺脲类受体基因多态性与新疆地区2型糖尿病相关性研究

目的　研究磺脲类受体 (sulfonylureareceptor,SUR1)基因第 2 4内含子 3tc多态性与新疆地区 2型糖尿病的相关性。方法　利用PCR -RFLP法对新疆地区 72例受试者 (2型糖尿病患者 4 2例 ,正常对照 30例 )磺脲类受体基因第 2 4内含子 - 3t→c多态性进行研究。结果　SUR1基因第 2 4内含子“c”等位基因频率在患者及对照中无显著差异 (77 5 %比 6 3 5 % ,P =0 0 6 5 3) ,“cc”基因型频率分别为 6 1 9% ,4 0 % ,也无显著差异 (P =0 0 6 6 2 )。结论　SUR1基因第 2 4内含子 - 3t→c多态性可能在新疆地区 2型糖尿病发病中不起重要作用。     

CDKAL1基因rs4712523多态性与内蒙古地区汉族人群2型糖尿病相关

目的 研究内蒙古地区汉族人群CDKAL1基因rs4712523单核苷酸多态性(SNP)的等位基因和基因型频率分布与2型糖尿病(T2DM)的相关性.方法 采用等位基因特异性聚合酶链式反应(AS-PCR),对382例内蒙古地区汉族人(其中T2DM组192例,对照组190例)rs4712523进行基因分型.结果 T2DM组中rs4712523的G等位基因频率和GG基因型频率分别为47.4％和6.3％,均显著高于对照组的35.3％和3.2％(P＜0.05).G等位基因携带者患T2DM的风险是A等位基因的1.654倍(OR=1.654,95％ CI=1.237-2.212).结论 CDKAL1基因rs4712523多态性位点的G等位基因可能是内蒙古地区汉族人T2 DM的易感基因之一.     

Association between the three functional miR-146a single-nucleotide polymorphisms,rs2910164, rs57095329, and rs2431697, and autoimmune disease susceptibility: A meta-analysis

Studies suggest associations between the miR-146a single nucleotide polymorphisms (SNPs) and susceptibility to autoimmune diseases. However, the results are inconsistent and inconclusive. Therefore, the aim of this study was to arrive at a conclusion about the association between the three functional miR-146a SNPs and autoimmune disease risk. Studies were identified through PubMed/MEDLINE searches for studies published up to January 2016 using as keywords rs2910164, rs57095329, rs2431697, and miR-146a polymorphisms. Thirty studies were included in the meta-analysis. The SNP rs2910164?G?>?C was found to be associated with increased risk of multiple sclerosis (CC?+?CG versus GG, OR = 1.25, 95% CI: 1.01–1.55), with decreased risks of psoriasis (C versus G, OR = 0.81, 95% CI: 0.69–0.96; CC versus GC?+?GG, OR = 0.73, 95% CI: 0.56–0.94), Behcet’s disease (CC versus GC?+?GG, OR = 0.60, 95% CI: 0.50–0.73), asthma (C versus G, OR = 0.80, 95% CI: 0.69–0.93; CC versus GC?+?GG, OR = 0.65, 95% CI: 0.48–0.86), and uveitis (CC?+?CG versus GG, OR = 0.61, 95% CI: 0.49–0.77). The SNP rs2431697 C?>?T was found to be associated with an increased risk of SLE (T versus C, OR = 1.26, 95% CI: 1.15–1.38; TC?+?TT versus CC, OR = 1.28, 95% CI: 1.03–1.58; TT versus TC?+?CC, OR = 1.40, 95% CI: 1.21–1.62). The SNP rs57095329 A?>?G was found to be associated with an increased risk of SLE (G versus C, OR = 1.25, 95% CI: 1.17–1.35). The miR-146a SNPs rs2910164, rs57095329, rs2431697 are associated with susceptibility to certain autoimmune diseases. However, for other autoimmune diseases, they may be protective or insignificant.     

Impact of miR-SNP rs2910164 on miR-146a expression in osteoarthritic chondrocytes

PurposeMiR-146a acts as a negative inflammatory mediator in different diseases and has been implicated in osteoarthritis (OA) pathogenesis. In our study, we investigated the association between miR-SNP rs2910164 and OA susceptibility and its role on the expression of miR-146a, inflammatory and catabolic mediators in osteoarthritic chondrocytes.Materials and methodsGenetic association analysis was performed in 1688 knee OA patients and healthy individuals of Greek origin. Genomic DNA was extracted from blood and genotyped for rs2910164 (G > C) using Restriction-Fragment Length Polymorphism (RFLP). Total RNA was extracted from chondrocytes of 18 OA patients and miR-146a, IL-1 Receptor-Associated Kinase 1 (IRAK-1), TNF Receptor-Associated Factor 6 (TRAF-6), A Disintegrin and Metalloproteinase with Thrombospondin Motifs 5 (ADAMTS-5), Matrix Metalloproteinase-13 (MMP-13), Interleukin-6 (IL-6), Interleukin-1 Beta (IL-1β) and Tumor Necrosis Factor-Alpha (TNF-α) expression was evaluated using quantitative Real-Time PCR (qRT-PCR).ResultsOA patients carrying rs2910164-GC and CC genotypes did not have an increased risk for OA development compared to GG genotype carriers. MiR-146a expression in OA chondrocytes was significantly lower in patients with rs2910164-GC genotype than in the GG carriers. OA patients carrying the rs2910164-GC genotype in their chondrocytes exhibited increased IRAK-1, TRAF-6, MMP-13, IL-1β and IL-6 expression levels compared with rs2910164-GG carriers.ConclusionWe demonstrate, for the first time, that miR-SNP rs2910164 in miR-146a gene is associated with reduced miR-146a and increased inflammatory and catabolic mediators’ expression in OA chondrocytes. Our data imply that genetic variations in miRNAs linked to OA pathogenesis may regulate their expression levels, suggesting new therapeutic strategies for patients with cartilage diseases.     

Predictive role of miR-146a rs2910164 (C>G), miR-149 rs2292832 (T>C), miR-196a2 rs11614913 (T>C) and miR-499 rs3746444 (T>C) in the development of hepatocellular carcinoma

We conducted a case-control study to evaluate the association of miR-146a rs2910164 (C>G), miR-149 rs2292832 (T>C), miR-196a2 rs11614913 (T>C) and miR-499 rs3746444 (T>C) polymorphisms with the risk of hepatocellular carcinoma. A total of 274 patients with HCC were collected between January 2013 and December 2014. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was taken to determine the polymorphism of miR-146a C>G, miR-149 T>C, miR-196a2 T>C and miR-499 T>C. By comparing with control groups, patients with HCC were more likely to be males (OR=2.01, 95% CI=1.38-2.95), have older age (OR=1.52, 95% CI=1.09-2.13), have a history of alcohol drinking (OR=2.09, 95% CI=1.49-2.93), and be infected with HBV (OR=32.98, 95% CI=19.70-55.46) and HCV (OR=56.26, 95% CI=23.28-152.98) infection. By conditional regression analysis, individuals carrying the TC and CC genotypes of miR-196a2 T>C were found to be associated with an elevated risk of HCC compared to the TT genotype, and the adjusted odds ratio were 1.50 (1.03-2.17) and 2.86 (1.60-5.16), respectively. Moreover, the TC+CC genotype was correlated with an increased risk of HCC (OR=1.69, 95% CI=1.19-2.41) compared to the wide-type genotype. In conclusion, our results suggested that miR-196a2 T>C polymorphism is associated with HCC risk in Chinese population.     

Association between miRNA-146a rs2910164 (G/C) polymorphism with the susceptibility to chronic HBV infection and spontaneous viral clearance in an Iranian population

Hepatitis B virus (HBV) infection is one of the clinical dilemmas in chronic liver diseases. MicroRNAs (miRNAs) are small noncoding RNA molecules that play an important role in the pathogenesis of liver diseases and single nucleotide polymorphisms (SNPs) in miRNA genes affect the clinical course of HBV infection. Previous studies have shown that miRNA-146a rs2910164 polymorphism can be associated with the pathogenesis of liver diseases such as hepatocellular carcinoma. The present study investigated the association between miRNA-146a rs2910164 polymorphism and susceptibility to HBV infection in an Iranian population. The study comprised 266 patients with chronic HBV infection, 172 patients with spontaneous viral clearance (SVC) after acute HBV infection, and 266 healthy control adjusted for sex and age. The genotyping of the miRNA-146a rs2910164 polymorphism was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Our data revealed that GG genotype and G allele of miRNA-146a rs2910164 SNP is dominated (P < 0.001) in patients with chronic HBV infection (Odds ratio [OR] = 3.92; 95% confidence interval [CI] = 2.1-7.32). miRNA-146a rs2910164 polymorphism showed a statistically significant association (P < 0.001) between CC genotype and allele C with SVC (OR = 2.92; 95% CI = 1.56-546). Our findings suggest miRNA-146a SNP (C/G) in our population may be associated with the susceptibility to HBV infection and CC genotype is associated with SVC. Also, the GG genotype and G allele at miRNA-146a rs2910164 is associated with chronic HBV infection in our population.     

Association of two polymorphisms rs2910164 in miRNA-146a and rs3746444 in miRNA-499 with rheumatoid arthritis: A meta-analysis

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.     

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

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

MicroRNA 146a基因单核苷酸多态性与卵巢上皮性肿瘤易感性的研究

目的 分析microRNA 146a(miR-146a)基因单核苷酸多态(single nucleotide polymorphisms,SNPs)位点rs2910164(G/C)与卵巢上皮性肿瘤易感性的关系.方法 采用病例-对照研究方法,纳入卵巢上皮性肿瘤患者184例为病例组,无卵巢肿瘤病史的人群200例为对照组.使用基因测序方法确定miR-146a基因rs2910164 (G/C)位点的多态基因型,比较不同基因型在病例组和对照组中的分布情况,并对年龄、月经周期、产次、口服避孕药、家族病史因素进行分层研究.结果 在miR-146a基因多态位点rs2910164(G/C)处,病例组和对照组均有GG、GC和CC 3种基因型,且两组的基因型总体分布差异具有统计学意义(P=0.002).与CC基因型相比,GG和GC基因型携带者的卵巢上皮性肿瘤发病风险较低(OR=0.396,95％ CI=0.219～0.717,P=0.002;OR=0.502,95％ CI =0.308～0.818,P=0.006).分层分析显示,这种影响在年龄≤50岁、产次≤2、未口服避孕药、无家族病史的情况下差异显著,x2检验P值分别为:0.001、0.000、0.001、0.001.结论 miR-146a单核苷酸多态位点rs2910164(G/C)与卵巢上皮性肿瘤易感性相关.GG和GC基因型携带者患卵巢上皮性肿瘤的发病风险低于CC基因型携带者.