MTRR基因G66A多态性与冠心病相关性的Meta分析

目的探讨甲硫氨酸合成酶还原酶(methionine synthase reduetase,MTRR)基因C66A多态性与冠心病易感性的相关性。方法从数据库Pub Med、Medline、CNKI及Wan Fang Data网站上检索并收集相关人群MTRR基因G66A多态性与冠心病风险的病例-对照研究,检索时限截至2017年12月。按照纳入与排除标准筛选文献、提取资料并评价纳入研究的质量后,用Stata 12.0软件进行Meta分析、发表偏倚评估和敏感性分析。结果共获得14篇相关文献,7篇纳入研究。MTRR G66A基因多态性与冠心病易感性相关研究中,共有冠心病患者1212例,对照组777例。MTRR C66A基因多态性与冠心病相关性经Meta分析结果显示在5个遗传模型中只有隐性遗传模型提示MTRR基因多态性与心血管疾病发病风险的相关性具有统计学意义。等位基因模型(G vs.A:OR=0.84,95%CI=0.925-1.210,P=0.398;Pheterogeneity=0.001,I2=72.8%);纯合子模型(GG vs.AA:OR=0.87,95%CI=0.850-1.523,P=0.385;Pheterogeneity=0.001,I2=78.1%);杂合子模型(GA vs.AA:OR=0.98,95%CI=0.861-1.115,P=0.758;Pheterogeneity=0.007,I2=66.5%);显性遗传模型(GG+GA vs.AA:OR=0.1,95%CI=0.906-1.115,P=0.923;Pheterogeneity=0.001,I2=74.2%);隐性遗传模型(GG vs.AA+GA:OR=3.02,95%CI=1.095-1.531,P=0.003;Pheterogeneity=0.102,I2=43.3%)。结论 MTRR基因G66A多态性与冠心病易感性相关,暴露因素GG可能是冠心病易感的危险因素。     

动脉硬化性脑梗死与肿瘤坏死因子α-238及肿瘤坏死因子α-308基因多态性的关系

目的 探讨肿瘤坏死因子(TNF)α-238及TNFα-308基因多态性与动脉硬化性脑梗死的关系.方法 运用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术检测97例动脉硬化性脑梗死(CI组)及141例正常人(对照组)的外周血TNFα-238、TNFα-308基因多态性AA、AG、GG的基因型.结果 CI组TNFα-238 GG、GA和AA基因型频率分别为88.66%、11.34%和0;对照组分别为95.74%、4.26%和0.CI组TNFα-238 G、TNFα-238 A基因频率分别为94.33%、5.67%;对照组分别为97.87%、2.13%.TNFα-238各种基因型频率在CI组与正常对照组之间的差异有统计学意义(均为P<0.05).CI组TNFα-308 GG、GA和AA基因型频率分别为77.32%、8.25%和14.43%;对照组分别为92.20%、5.67%和2.13%.CI组TNFα-308 G、TNFα-308 A基因频率分别为81.44%、18.56%;对照组分别为95.04%、4.96%.TNFα-308各种基因型频率在CI组与正常对照组之间的差异有统计学意义(均为P<0.05).结论 TNFα-238和TNFα-308基因多态性AA、AG、GG基因型与CI有关联.     

肿瘤坏死因子-α基因启动子多态性与慢性乙型肝炎易感性的关系

目的探讨湖北汉族人肿瘤坏死因子-α(TNF-α)基因启动子多态性及其与慢性乙型肝炎易感性之间的关系。方法应用聚合酶链反应-限制性片段长度多态性分析方法(RFLP),检测126名正常对照者和131例慢性乙型肝炎患者TNF-α基因启动子多态性。结果共发现12种启动子基因型,以GG.GG.CC.CC、GG.GG.CC.CA、GG.GG.CT.CC和GG.GA.CC.CC基因型多见,约占85%;通过对TNF-α基因启动子4个位点基因型分析发现,慢性乙型肝炎患者和正常对照者TNF-α基因启动子-238G/A、-857C/T位点基因型分布频率差异无显著性,而-308G/A、-863C/A位点基因型分布频率差异有显著性。结论湖北汉族人慢性乙型肝炎易感性与TNF-α基因启动子-308G/A、-863C/A位点多态性有关,其中TNF-α-308GA、-863CA基因型携带者患慢性乙型肝炎风险相对较小。     

TNF-α-238G/A基因多态性与原发性肝癌的关系

目的 探讨肿瘤坏死因子-α（TNF-α）基因启动子-238G/A多态性与原发性肝癌（PHC）的相关关系.方法 应用聚合酶链反应-限制性片段长度多态性法（PCR-RFLP）检测100例PHC患者和150例健康对照者TNF-α基因启动子-238G/A多态性.结果 TNF-α-238基因型GG、GA频率在PHC组和对照组分别为95.3%和4.7%,88%和12%;等位基因G、A频率在PHC组和对照组分别为97.7%和4.7%,94%和6%.两组差异均有显著性（P＜0.05）,携带GA基因型个体患PHC的风险约是GG基因型的2.786倍（OR=2.786,95%CI=1.057～7.343）.结论 TNF-α-238G/A基因多态性与PHC的发病有相关性,A等位基因可能是PHC的遗传易感基因.     

内蒙古包头地区汉族人群TNF-α-308位点基因多态性与IgA肾病的相关性研究

目的：了解内蒙古包头地区汉族人群IgA肾病患者肿瘤坏死因子α（TNF-α）-308位点基因型的分布特点。方法：应用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）技术检测97例IgA肾病患者和73例正常人的TNF-α基因型。结果：IgA肾病患者组中TNF-α基因G/A多态GG、GA、AA基因型频率分别为85.6%、11.3%和3.1%,其中G和A等位基因频率分别为91.2%和8.8%。正常对照组中,TNF-α基因G/A多态GG、GA、AA基因型频率分别为91.8%、5.5%和2.7%,其中G和A等位基因频率分别为94.5%和5.5%。IgA肾病患者组与正常对照组比较,基因型频率差异有显著性（χ^2=27.2,P〈0.05）,等位基因频率之间差异无显著性（χ^2=0.659,P〉0.05）。结论：TNF-α-308位点基因多态性与内蒙古包头地区汉族人群IgA肾病的发病有相关性,等位基因频率之间差异无显著性（χ^2=0.659,P〉0.05）。     

肿瘤坏死因子α-308基因多态性与牙周病相关性

目的探讨肿瘤坏死因子-α308位点基因多态性与牙周炎易感性的关系。方法采用序列特异引物PCR方法 （SSP-PCR）方法检测了78例重度慢性牙周炎（CP）患者和70例健康对照组的TNFα-308（G/A）位点基因多态性。结果 CP患者TNFα-308各基因型（GG,GA,AA）频率分别为70.5%、0%和29.5%,在对照者中分别为67%,3%和30%二组之间的基因型频率分布的比较,差异没有显著性（χ2=2.29,P〉0.05）;GG和AA的等位基因频率在CP中分别85.3%和14.7%,在对照者中分别为82%和18%,二者之间比较,差异没有显著性（χ2=0.526,P〉0.05）。结论 TNF-α-308基因多态性位点可能不是中国人患牙周病的主要易感位点基因。     

NKX2.5基因63A>G多态性与先天性心脏病相关性的Meta分析

目的探讨NKX2-5基因63AG多态性与先天性心脏病易感性的关系。方法从数据库Pub Med、Medline、CNKI及WanFangData网站上检索并收集相关人群NKX2-5基因63AG多态性与先天性心脏病易感性的病例-对照研究,检索时限截至2018年3月。按照纳入与排除标准筛选文献、提取资料并评价纳入研究的质量后,用Stata12.0软件进行Meta分析、发表偏倚评估和敏感性分析。结果共10篇纳入研究。NKX2-5基因63AG多态性与先天性心脏病易感性相关研究中,共有先心病患者1725例,对照组1650例。经Meta分析结果显示NKX2-5基因63AG多态性与先天性心脏病的相关性在5个遗传模型中都没有统计学意义(P0.05)。等位基因模型(Gvs.A:OR=1.028,95%CI=0.945-1.117,P=0.524;P_(heterogeneity)0.001,I2=75.5%);显性遗传模型(GG+GA vs. AA:OR=1.006,95%CI=0.949-1.066,P=0.845;P_(heterogeneity)0.001,I2=71.1%);隐性遗传模型(GG vs. AA+GA:OR=1.056,95%CI=0.968-1.152,P=0.222;P_(heterogeneity)=0.119,I2=36.2%);纯合子模型(GGvs.AA:OR=1.009,95%CI=0.915-1.112,P=0.863;P_(heterogeneity)=0.008,I2=59.9%);杂合子模型(GAvs.AA:OR=1.001,95%CI=0.918-1.092,P=0.978;P_(heterogeneity)=0.010,I2=58.7%)。结论 NKX2-5基因63AG多态性可能不是先天性心脏病的危险因素。     

足月前胎膜早破患者肿瘤坏死因子α基因多态性及羊水中表达分析

目的探讨肿瘤坏死因子-α(TNF-α)基因启动子区-308位点单核苷多态性(single nucleotide polymorphism,SNP)及其羊水中TNF-α水平与足月前胎膜早破(PPROM)发病的关系。方法收集100名PPROM患者、150名正常足月分娩患者外周血,提取基因组DNA,进而采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析方法检测TNF-α基因-308位点SNP的基因型。其中71例PPROM和50例正常足月分娩患者同时收集到羊水样本。采用双抗体夹心酶联免疫吸附试验(ELISA)方法检测羊水中TNF-α浓度;结果 1.研究结果显示:PPROM组与正常对照组比较:TNF-α-308位点TNF-α基因启动子区-308位点GG/GA+AA基因型分布及G/A等位基因频率均存在显著性差异,(均P0.05)。2.PPROM组羊水中TNF-α浓度为104.25±8.71明显高于正常对照组(70.18±9.03),两组TNF-α浓度有统计学差异(P=0.000)。3.A等位基因携带(即G/A+A/A基因型携带者)TNF-α浓度为105.42±7.76明显高于G/G基因型携带者(69.21±8.87),两者比较有显著性差异(P=0.000)。结论 1.羊水中TNF-α浓度明显升高是胎膜早破发病的重要机制中之一;2.TNF-α-308位点SNP与TNF-α的表达有关,携带-308A等位基因可使羊水中TNF-α高表达,是PPROM患病的易感基因。     

细胞毒T淋巴细胞相关蛋白4(CTLA4)基因多态性与非霍奇金淋巴瘤易感性的meta分析

目的探讨细胞毒T淋巴细胞相关蛋白4(CTLA4)等位基因多态性与非霍奇金淋巴瘤(NHL)易感性的关系。方法计算机检索Pub Med、MEDLINE、中国知网、万方及维普等数据库,收集1990-01-01/2016-05-25期间CTLA4基因多态性与NHL易感性关系的研究资料。采用SATA(v12.0)软件进行meta分析,计算比值比(OR)及其95%可信区间(CI)并行敏感性分析和发表偏倚评估。结果共纳入6项研究,涉及CTLA4+49A/G、-318T/C、CT60 A/G 3个等位基因,NHL患者803例,对照共1254例。这3个等位基因多态性与NHL的易感性无相关性(PZ0.05或95%CI包含1)。在CTLA4+49A/G基因多态性的亚组分析中却发现携带AA是HNL混合型的危险因素(AA vs GG:OR=4.181,95%CI:1.362~12.833;AA+AG vs GG:OR=3.217,95%CI:1.055~9.810;AA vs AG+GG:OR=2.827,95%CI:1.345~5.940),然而在B细胞淋巴瘤中是保护因素(AA vs GG:OR=0.465,95%CI:0.251~0.863;AA vs AG+GG:OR=0.534,95%CI:0.362~0.788);携带AA也是意大利人的危险因素(AA vs GG:OR=4.181,95%CI:1.362~12.833;AA+AG vs GG:OR=3.217,95%CI:1.055~9.810;AA vs AG+GG:OR=2.827,95%CI:1.345~5.940),但在中国人中是保护因素(AA vs GG:OR=0.643,95%CI:0.417~0.992;AA vs AG+GG:OR=0.601,95%CI:0.395~0.913)。结论 CTLA4+49A/G、-318T/C、CT60 A/G3个等位基因多态性与NHL易感性无明显关联性。     

妊娠期糖尿病患者肿瘤坏死因子-α基因多态性的实验性研究

目的研究东北汉族妊娠期糖尿病(GDM)孕妇肿瘤坏死因子-α(TNF-α)基因多态性的分布频率及在GDM发病中的作用.方法选取120例GDM作为病例组,120例糖耐量正常的孕妇作为对照组,采用双抗体夹心酶联免疫吸附试验(ELISA)检测血清TNF-α水平,以稳态模型Homa model公式评估胰岛素抵抗(IR),同时应用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)技术,检测TNF-α基因-308和-238位点等位基因和基因型的分布频率.结果⑴ GDM组及对照组的血清TNF-α水平分别为(10.29±2.44) μg/L 和(5.21±1.01) μg/L (P＜0.05);FINS分别为(24.34±12.84 ) mIU/L 和(17.88±7.31 ) mIU/L(P＜0.01);HOMA-IR分别为(2.74±1.06) 和(1.35±0.69) (P＜0.01).⑵GDM组-238多态性位点A等位基因频率(0.0583和0.0417)及GA AA基因型频率(0.1083和0.0917)均高于正常妊娠对照组,但差异无统计学意义(P＞0.05).GDM组-308多态性位点A等位基因频率(0.1375和0.0583)及GA AA基因型频率(0.2417和0.1167)显著高于正常妊娠对照组,差异有统计学意义(P＜0.05).⑶GDM组GA AA基因组及GG基因型组TNF-α分别为[(6.35±1.43) μg/L]和[(5.68±0.45) μg/L] (P＜0.05);FINS分别为(13.42±4.73) mIU/L和(10.40±3.63) mIU/L(P＜0.01);HOMA-IR分别为(7.42±1.93)和(4.11±1.31)(P＜0.01).结论我国东北汉族孕妇人群中,TNF-α基因 308G→A变异可增加孕妇患妊娠期糖尿病的危险性.A等位基因可能通过增加TNF-α的释放参与胰岛素抵抗,导致GDM的发病.     

Meta-analysis of TNF-α promoter − 238A/G polymorphism and SLE susceptibility

The tumor necrosis factor-α (TNF-α) promoter ? 238A/G polymorphism has been repeatedly associated with systemic lupus erythematosus (SLE), but findings are not consistent across studies. Our aim was to do a meta-analysis to assess the association between TNF-α promoter ? 238A/G polymorphism and SLE. Eleven published studies of this polymorphism with SLE in different ethnic groups were identified using a Medline search. Meta-analysis was performed for genotypes AA versus GG, GA versus GG, AA versus GG+GA, GA+AA versus GG, and A allele versus G allele in a fixed/random effect model. The overall odds ratio (OR) of the AA versus GG+GA genotypes was 3.46 (95% CI = 1.35–8.83, P = 0.01), and a similar result was found in Caucasian population (OR = 4.62, 95% CI = 1.20–17.80, P = 0.03); the overall OR of the AA versus GG genotypes was 3.36 (95% CI = 1.32–8.55, P = 0.01), and a similar result was found in Caucasian population (OR = 4.29, 95% CI = 1.11–16.53, P = 0.03); the OR of the GA versus GG genotypes was 0.48 (95% CI = 0.30–0.75, P = 0.001) in Caucasian population. In conclusion, this meta-analysis demonstrates the association between TNF-α promoter ? 238A/G polymorphism and SLE, especially in Caucasian population.     

The relationship between tumour necrosis factor-α gene polymorphism and susceptibility and clearance of the persistent hepatitis B virus infection in a Chinese population: a meta-analysis

To date, many studies conducted in the Chinese population have determined the correlation between the tumour necrosis factor-α (TNF-α)-238G/A, -308G/A, -857C/T and -863C/A polymorphisms and persistent hepatitis B virus (HBV) infection. However, their results remain inconclusive. With the aim of confirming this correlation, we performed a meta-analysis of 19 studies. The dichotomous data are presented as the OR with a 95% CI. The results of our study indicate that carriers of the TNF-a-857T allele among the pooled Chinese population were more likely to show spontaneous clearance of HBV (T vs C: OR = 0.824, 95% CI = 0.713–0.953, p 0.009; TT vs CC: OR = 0.701, 95% CI = 0.507–0.970, p 0.032; TC vs CC: OR = 0.804, 95% CI = 0.683–0.947, p 0.009; TT + TC vs CC: OR = 0.835, 95% CI = 0.716–0.974, p 0.021). The TNF-a-308A allele was associated with significantly reduced persistent HBV infection risk in the Chinese (A vs G: OR = 0.585, 95% CI = 0.456–0.751, p 0.002; AG vs GG: OR = 0.519, 95% CI = 0.341–0.789, p <0.000; AA + AG vs GG: OR = 0.512, 95% CI = 0.339–0.772, p 0.001). Persistent HBV infection susceptibility is associated with the TNF-α-308G/A gene polymorphism in the Chinese population, whereas HBV clearance is associated with the TNF-α-857C/T gene polymorphism.     

Association of tumour necrosis factor-alpha -308 G/A promoter polymorphism with susceptibility and disease profile of rheumatoid arthritis

The objective was to analyze the possible involvement of tumour necrosis factor-alpha (TNF-α) -308 G/A promoter polymorphism in the susceptibility and/or the disease profile of rheumatoid arthritis (RA) in Egyptian patients. TNF-α-308 G/promoter polymorphism detection by amplification refractory mutation system (ARMS) technique was carried out for 122 RA patients and 120 healthy controls. TNF-α-308 G allele/GG homozygous genotype were higher in patients with rheumatoid arthritis than those in control group (P < 0.001, respectively). A statistically significant association was found between the frequency of the A allele and presence of erosion (OR = 3.42, P = 0.015). No associations were found between the distribution of TNF-α-308 G/A alleles/genotypes and age of patients, disease duration, absence of remission, presence of deformity, clinical manifestations of the disease and presence or absence of rheumatoid factor. The positivity of rheumatoid factor was associated with occurrence of erosion (OR = 25.0, P < 0.001). The results of this study demonstrate the association of the TNF-α-308 G allele and GG homozygous genotype with susceptibility to RA and the A allele with the presence of erosion in the Egyptian patients.     

Tumour necrosis factor alpha -308G/A polymorphism and risk of the four most frequent cancers: a meta-analysis

The latest data show that breast, prostate, lung and colorectal cancer are the four most frequent cancers in both sexes worldwide. A number of molecular epidemiological studies have been conducted to examine the association between TNF alpha -308G/A and the risk of those cancers. However the results have been inconclusive or inconsistent. We then performed a meta-analysis to derive a precise estimation of this association. We carried out a comprehensive search in Medline, EMBASE, OVID and Chinese Biomedical Literature Database for studies using related keywords. The inclusion criteria were (i) in English or Chinese; (ii) case-control study on this association; (iii) provide usable genotype frequencies; and (iv) sufficient published data for estimating an odds ratio (OR) with 95% confidence interval (CI). ORs and 95% CIs were calculated to assess the strength of this association under homozygote comparison (AA vs GG), heterozygote comparison (GA vs GG), dominant (AA/GA vs GG) and recessive (AA vs GA/GG) genetic model comparison. Thirty case-control studies with a total number of 16,507 cases and 19,749 controls were selected for analysis. Overall, no significant association was found between this polymorphism and the risk of total four cancers (GA vs GG: OR=1.02, 95% CI=0.91-1.14, P=0.78). However, there was a significant association between this polymorphism and breast cancer risk in western populations (GA vs GG: OR=0.91, 95% CI=0.85-0.96, P=0.002). This meta-analysis also revealed that this polymorphism was not associated with susceptibility to the other three cancers.     

Investigation on the association between inerleukin-10 -592C/A, 819C/T and -1082A/G gene polymorphisms and development of diabetic nephrophathy

We conducted a case-control study to investigate the association between interleukin (IL)-10-592C/A, -819C/T and -1082A/G polymorphisms and susceptibility to diabetic nephropathy. A hospital-based case-control study was taken in our study. A total of 172 patients with proven type 2 diabetes mellitus and 344 controls were recruited from the First Affiliated Hospital of Xinxiang Medical University between March 2012 and October 2014. Genotyping of IL-10 -592C/A, -819C/T and -1082A/G polymorphisms was done by done by PCR-RFLP methods. By the χ² test, the distributions of the GG, GA and AA genotypes in IL-10 -1082A/G were significantly different between patients with diabetic nephropathy and control subjects (χ² = 8.09, P = 0.02). By conditional logistic regression analysis, we found that the AA genotype of IL-10 -1082A/G was associated with an elevated risk of diabetic nephropathy compared to the GG genotype in codominant model, and the adjusted OR (95% CI) was 2.38 (1.23-4.57). In dominant model, the GA+AA genotype was associated with a significantly increased risk of diabetic nephropathy compared to the GG genotype in dominant model (OR = 1.47, 95% CI = 1.05-2.16). In recessive model, the AA genotype could influence the susceptibility to diabetic nephropathy when compared with the GG+GA in recessive model (OR = 2.08, 95% CI = 1.12-3.85). In conclusion, we suggested that IL-10 -1082A/G gene polymorphism was correlated with development of diabetic nephropathy, but no association was observed between IL-10 -819T/C and -592A/C and risk of diabetic nephropathy.     

Relationship between the polymorphism of tumor necrosis factor-α-308 G>A and susceptibility to inflammatory bowel diseases and colorectal cancer: a meta-analysis

Inflammatory bowel disease (IBD) and colorectal cancer (CRC) are common health problems worldwide. Tumor necrosis factor (TNF) is a type of cytokine that induces inflammation and inhibits tumorigenesis. Several studies have assessed the relationship between the polymorphism of TNF-α-308 G>A and the susceptibility to IBD and CRC; however, the results have been controversial. In addition, the hypothesis whether the increased risk of CRC in IBD patients could be partly ascribed to the polymorphism of TNF-α-308 G>A was unclear. Therefore, we conducted this meta-analysis to confirm these associations. Pooled odd ratios (ORs) and 95% confidence intervals (95% CIs) were calculated on the basis of data from 14, 18, and 7 studies from a total of 27 studies for the associations between the polymorphism of TNF-α-308 G>A and ulcerative colitis, Crohn's disease (CD) and CRC. In Europeans, the AA genotype increased the risk of ulcerative colitis (UC) (OR, 2.041; 95% CI, 1.261-3.301) and CD (OR, 1.730; 95% CI, 1.168-2.564) significantly, without obvious heterogeneity and publication bias. Meanwhile, the GA genotype increased the risk of UC in Asians (OR, 2.360; 95% CI, 1.269-4.390) significantly. However, no significant association was observed for CRC in any ethnic population. The results of this meta-analysis suggested that the polymorphism of TNF-α-308 G>A participates in modifying the susceptibility to UC and CD in Europeans and Asians. The increased risk of CRC in IBD patients should be clarified as the combined effects of polymorphisms in TNF-α and other cytokines, and the interaction with environmental factors, in future studies.     

Tumor necrosis factor‐α −308G/A and −238G/A polymorphisms are associated with increased risks of sepsis: evidence from an updated meta‐analysis

Previous studies have reported the relationship between tumor necrosis factor‐α (TNF‐α) ?308G/A and ?238G/A polymorphisms and sepsis risk with inconsistent results. The aim of this study was to estimate the association of the two polymorphisms with risk of sepsis or sepsis‐related mortality using a meta‐analysis. PubMed, Embase, and Web of Science databases were searched up to June 20 2016. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using fixed or random effect model. Twenty‐six studies were included in this meta‐analysis. Overall, an increased sepsis risk of TNF‐α ?308G/A was observed (GA vs GG: OR = 1.43, 95% CI: 1.07–1.92; GA/AA vs GG: OR = 1.42, 95% CI: 1.06–1.89). Subgroup analyses showed that the significant association was found in Asians (GA vs GG: OR = 1.63, 95% CI: 1.01–2.63) and adult patients. Similarly, an increased sepsis risk of TNF‐α ?238G/A was observed in overall and subgroup analyses. However, no significant association was found between TNF‐α ?308G/A and ?238G/A polymorphisms and sepsis‐related mortality. These findings indicate that both TNF‐α ?308G/A and ?238G/A polymorphisms were associated with increased risks of sepsis but not sepsis‐related mortality. Further studies with larger sample size are needed to confirm these results.