CTLA-4基因49位点A/G多态性与原发性胆汁性肝硬化的Meta分析

目的采用Meta分析系统评价细胞毒性T淋巴细胞相关抗原-4（CTLA-4）基因外显子上49位点A/G多态性与原发性胆汁性肝硬化的关联性。方法计算机检索Pubmed、EMBASE、Medline、中国期刊全文数据库、万方等中英文数据库,获取CTLA-4基因49位点A/G多态性与原发性胆汁性肝硬化易感性的独立患者-对照研究。以原发性胆汁性肝硬化组与对照组人群基因型分布的OR值为效应指标,采用固定或随机效应模型进行合并分析,并进行偏倚评估。应用RevMan5.0软件进行统计学处理。结果共纳入文献7篇,累计原发性胆汁性肝硬化组1 106例,健康对照组2 243例。Meta分析结果表明,总研究原发性胆汁性肝硬化人群CTLA-4基因49G等位基因OR值为1.21,95%CI为1.07～1.34,差异有统计学意义（P〈0.05）;基因G/G的OR值为1.30,95%CI为1.01～1.65,差异有统计学意义（P〈0.05）;基因A/A的OR值为0.82,95%CI为0.71～0.95,差异有统计学意义（P〈0.05）。分层分析显示,亚洲原发性胆汁性肝硬化人群CTLA-4基因49G等位基因OR值为1.67,95%CI为1.20～2.32,差异有统计学意义（P〈0.05）;基因G/G的OR值为2.00,95%CI为1.22～3.29,差异有统计学意义（P〈0.05）;基因A/A的OR值为0.51,95%CI为0.25～1.06,差异无统计学意义（P〉0.05）。西方原发性胆汁性肝硬化人群CTLA-4基因49G等位基因OR值为1.18,95%CI为1.07～1.32,差异有统计学意义（P〈0.05）;基因G/G的OR值为1.23,95%CI为0.96～1.54,差异无统计学意义（P〉0.05）;基因A/A的OR值为0.83,95%CI为0.70～0.97,差异无统计学意义（P〉0.05）。经Begg’s检验所纳入研究未发现偏倚。结论 CTLA-4基因49位点A/G多态性等位基因与原发性胆汁性肝硬化人群易感性相关,CTLA-4基因49位点G等位基因与原发性胆汁性肝硬化人群易感性高于CTLA-4基因49位点A等位基因。     

CTLA-4和TGF-β1基因多态性与中国人大肠癌易感性研究

目的:探讨细胞毒性T淋巴细胞相关抗原4(CTLA-4)和转化生长因子β1(TGF-β1)基因多态性及单倍型与中国人大肠癌(CRC)易感性的关系.方法:提取451例大肠癌患者和420例健康对照者的外周血基因组DNA,采用聚合酶链反应-限制性片段长度多态性法(PCR-RFLP)检测CTLA-4 rs4553808、CTLA...     

Graves眼病与CTLA-4基因第1外显子A49G多态性及临床特点的相关性研究

目的：探讨Graves眼病患者与细胞毒性T淋巴细胞相关抗原-4（CTLA-4）基因第1外显子A49G多态性及临床特点的关系。方法：应用聚合酶链反应-限制性片段长度多态性技术测定107例Graves病患者（其中伴突眼50例，不伴眼病57例）CTLA-4基因第1外显子A49G多态性，分析其基因表型、基因频率与眼病的关系；并分析眼病与年龄、性别、甲状腺肿大程度、血清甲状腺球蛋白抗体（TgAb）、甲状腺过氧化物酶抗体（TPOAb）等临床相关因素的关系。结果：无眼病组（GH组）与伴突眼组（GO组）相比，GG基因型及等住基因G的频率差异均有显著性（P〈0．05），低TgAb可能是Graves病患者伴发突眼的危险因素（P〈0.05），而平均年龄、性别比例、甲状腺肿大程度以及血清TPOAb水平相比较则均无统计学差异（P〉0．05）。结论：GG基因型和等位基因G是Graves眼病的遗传易感因素，低TgAb促进Graves眼病的发生；而Graves眼病的发病与年龄、性别、甲状腺肿大程度以及血TPOAb水平可能无明显相关性。     

CTLA-4基因启动子区多态性与系统性红斑狼疮的关系分析

目的分析细胞毒性T淋巴细胞相关抗原-4(CTLA-4)基因启动子区-1722和-318位点多态性与系统性红斑狼疮(SLE)的关联性。方法利用聚合酶链反应-限制性片段长度多态性分析方法对112例患者和110例健康者检测-1722位点胸腺嘧啶/胞嘧啶(T/C)和-318位点T/C的多态性,并进行基因扩增,依据各条带相对分子质量的大小对CTLA-4基因-1722位点T/C和-318位点T/C进行分型。结果以组一为例,CTLA-4基因-1722位点TC基因型频率明显升高,差异有统计学意义(32%vs31%,P=0.015,OR=0.618);CC基因型频率明显升高,差异也有统计学意义(30%vs21%,P=0.039,OR=1.586);TT基因型频率虽有降低趋势,但差异无统计学意义(0%vs7%,P=0.346,OR=1.008),SLE组和健康对照组CTLA-4基因-1722位点等位基因C基因型频率明显升高,差异有统计学意义(61%vs68%,P=0.053,OR=1.781);携带者C基因型频率明显降低,差异也有统计学意义(52%vs59%,P=0.040,OR=1.652)。另外列出了CTLA-4基因-1722位点TC、CC和TT基因型的电泳结果及CTLA-4基因-318位点PCR单扩结果。结论 CTLA-4基因启动子区-1722的TC、CC基因可能是SLE易感性的一个危险因子,CTLA-4基因启动子区-1722基因型和CTLA-4基因启动子区-1722和-318位点的活性水平可作为推测SLE易感性的参考指标。     

sCTLA-4联合CEA、CA19-9检测对结直肠癌的诊断价值

目的探讨血清可溶性细胞毒性T淋巴细胞相关抗原-4(s CTLA-4)水平与结直肠癌(CRC)患者的临床病理的特征关系,评价其对CRC的诊断价值。方法收集111例CRC患者的术前血清及临床病理资料,以37例体检健康者作为健康对照组。ELISA法检测血清中s CTLA-4含量,分析其与临床病理特征的关系,并用受试者工作特征曲线(ROC)和二元Logistic回归比较s CTLA-4、CEA和CA19-9对CRC的诊断价值。结果 CRC患者血清中s CTLA-4含量显著高于健康对照组(t=9.37,P0.01);溃疡型腺癌s CTLA-4水平明显高于隆起型腺癌(t=2.40,P0.05);CEA单独检测特异性最高(97%),而s CTLA-4、CEA、CA19-9联合检测的准确性最高(91%)。结论血清s CTLA-4、CEA和CA19-9 3者联合检测在CRC诊断中具有较好的临床应用价值,可作为潜在的CRC辅助诊断方法。     

江苏地区汉族人群CTLA-4 rs4675369基因多态性与原发性胆汁性肝硬化的相关性

目的观察细胞毒性T淋巴细胞相关抗原-4(CTLA-4)rs4675369位点基因多态性与原发性胆汁性肝硬化(PBC)的关系。方法用分子量阵列技术对710例PBC患者和743例健康对照者CTLA-4 rs4675369位点进行多态性检测,分析两组人群中基因型及等位基因频率的分布情况,明确该基因位点是否为PBC易感位点。结果 PBC组GG基因型和G等位基因频率分别为28.3%和51.4%,均高于对照组的21.7%和46.4%,且差异均有统计学意义(P均0.05)。GG基因型比值比(OR)为1.43(95%CI:1.13~1.81),经年龄、性别因素校正后为1.43(95%CI:1.12~1.82)。结论江苏地区汉族人群CTLA-4rs4675369位点多态性与PBC存在相关性。     

SLE患者CTLA-4基因多态性与ANA、抗dsDNA抗体相关性研究

目的探讨细胞毒性T淋巴细胞相关抗原-4基因(CTLA-4)+49A/G多态性与SLE的相关性以及对ANA、抗dsDNA抗体的影响。方法采用PCR-限制性片段长度多态性(PCR-RFLP)技术分析92例SLE患者、60例健康对照的CTLA-4基因第一外显子+49基因型多态性,用间接免疫荧光法检测SLE患者ANA与抗dsDNA抗体。结果SLE患者中CTLA-4第一外显子+49 GG型显著高于对照组(P<0.05);92例SLE患者ANA阳性率87.0%,抗dsDNA阳性率为44.6%;ANA阳性组与阴性组的CTLA-4+49基因型分布无显著性差异(P>0.05),抗dsDNA阳性组与阴性组的CTLA-4+49基因型分布有显著性差异(P<0.05),抗dsDNA阳性SLE患者CTLA-4+49 GG型26例(63.4%),抗dsDNA阴性SLE患者,CTLA-4+49 GG型仅14例(27.5%),2组相差显著(P<0.01)。结论CTLA-4第一外显子+49A/G多态性与SLE显著相关,CTLA-4+49A/G多态性与SLE患者ANA无关联,与抗dsDNA抗体存在关联。     

细胞毒T淋巴细胞相关抗原4基因多态性与宫颈癌易感性的相关分析

目的分析细胞毒T淋巴细胞抗原4(CTLA-4)基因-318 T/C、CT60 G/A、+49 G/A多态性与宫颈癌易感性之间的关系。方法以292例宫颈癌患者及355例健康对照者作为研究对象。抽提全血基因组DNA,PCR扩增后用直接测序法检测CTLA-4基因-318 T/C、CT60 G/A、+49 G/A多态性;密度梯度离心法分离外周血单个核细胞(PBMCs),MTT法检测携带不同基因型的PBMCs的增殖能力;ELISA法检测各组血清中IL-2、IL-4、TGF-β的表达水平。结果与CTLA-4-318TT基因型相比,CC基因型降低宫颈癌的发病风险(χ2=7.440,P0.05);与CTLA-4 CT60GG基因型相比,AA基因型降低宫颈癌的发病风险(χ2=12.165,P0.05);携带CTLA-4-318 T、CT60 G等位基因的宫颈癌患者增加(χ2分别为13.482和14.138,P均0.05);而CTLA-4+49 G/A多态性与降低宫颈癌发病风险无关;携带CTLA-4-318TT、TC、CC的PBMCs细胞增殖率差异有统计学意义(F=13.842,P0.05),而携带CT60、+49不同基因型的PBMCs细胞增殖率差异无统计学意义(F分别为0.578、0.150,P均0.05)。CTLA-4-318 T/C、CT60 G/A、+49 G/A不同基因型间IL-2、IL-4和TGF-β的水平差异均有统计学意义(P均0.05)。对宫颈癌组分层分析发现,CTLA-4-318 T/C基因多态性与患者的年龄、绝经与否、HPV感染因素无关(χ2分别为6.310、1.362和4.772,P均0.05),而与肿瘤分期有关(χ2=18.555,P0.05)。结论 CTLA-4-318 T/C基因多态性与宫颈癌的患病风险及病情进展有关,其机制可能与调节T细胞的增殖及TH细胞因子的分泌有关。     

白细胞介素4基因多态性与结直肠癌的易感性

目的研究白细胞介素-4 (interleukin-4,IL-4)基因多态性与结直肠癌的相关性。方法采用聚合酶链式反应-序列特异性引物(PCR-SSP)方法及聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法检测93例结直肠癌患者及107例健康对照者的IL-4内含子3及启动子-589位点基因型。结果结直肠癌组IL-4内含子3的RP1基因频率明显低于对照组(69.9% vs 86.4%,χ2＝16.300,P<0.01),RP2基因频率明显高于对照组(30.1% vs 13.6%,χ2＝16.300,P<0.01)。RP1.1,RP1.2基因型的优势比值分别为0.28(95%CI,0.15～0.50)和3.28(95%CI,1.77～6.07)。IL-4-589位点在结直肠癌组和对照组中基因型分布和等位基因频率与内含子3位点频率分布一致,连锁不平衡。结论结直肠癌与IL-4基因多态性相关联。     

抵抗素基因多态性与结直肠癌易感性的相关性

目的 探讨抵抗素基因多态性与结直肠癌易感性的相关性。方法 选取56例结直肠癌患者为研究对象(病例组),选取同期52例结直肠腺瘤患者为对照组,选取同期60例健康体检者作为健康组。提取3组血清基因组DNA,采用聚合酶链反应(PCR)法扩增抵抗素基因rs1862513片段并进行基因测序,探究其基因多态性;采用酶联免疫吸附(ELISA)法检测血清抵抗素、脂联素和瘦素水平;比较3组抵抗素基因多态性位点rs1862513基因型分布;采用Logistic回归分析法分析影响结直肠腺癌发生的因素。结果 抵抗素基因在rs1862513位点上有GG型、GC型、CC型共3种基因型,健康组中GG型基因型最多,CC型基因型最少;对照组GC型基因型最多,CC型基因型最少;病例组CC型基因型最多,GG型基因型最少。病例组、对照组及健康组各基因型符合Hardy-Weinberg平衡定律(P>0.05)。病例组抵抗素水平低于健康组和对照组,脂联素、瘦素水平高于健康组和对照组,差异有统计学意义(P<0.05);对照组抵抗素水平低于健康组,脂联素、瘦素水平高于健康组,差异有统计学意义(P<0.05)。CC型...     

XRCC2 Arg188His polymorphism and colorectal cancer risk: a meta-analysis

ObjectiveTo investigate the potential correlation between the Arg188His (rs3218536) polymorphism of X-ray repair cross-complementing 2 (XRCC2) and colorectal cancer (CRC) risk, as the association remains unclear.MethodsThe CNKI, PubMed, EMBASE and Cochrane library databases were systematically searched for relevant studies published up to July 2021. Data were extracted from included studies, and analysed for pooled or subgroup odds ratios (ORs) with 95% confidence intervals (CIs) using STATA 12.0 software.ResultsSeven published studies were included. Pooled analysis revealed that the XRCC2 Arg188His polymorphism was associated with increased CRC risk (His versus Arg: OR 1.14, 95% CI 1.01, 1.29). Trial Sequential Analysis to test the power of the results showed that they were unreliable and the meta-analysis required additional studies.ConclusionThe current meta-analysis suggests that the XRCC2 Arg188His polymorphism may be a risk factor for CRC.     

Type 1 diabetes is insulin -2221 MspI and CTLA-4 +49 A/G polymorphism dependent

BACKGROUND: Several studies have demonstrated an association of type 1 diabetes with specific alleles of HLA class II molecules, as with polymorphisms of insulin gene region. The aim of our study was to evaluate the interaction of insulin -2221 MspI polymorphism to type 1 diabetes susceptibility in connection with autoimmunity associated gene--CTLA-4 polymorphism. MATERIALS AND METHODS: Insulin -2221 MspI C/T and CTLA-4 +49 A/G polymorphisms were detected by restriction fragment-length polymorphism analysis or oligonucleotide hybridization in type 1 (n = 69), type 2 diabetes (n = 301) patients and 158 healthy controls. Regression model adjusted for age, gender and gene polymorphisms was studied. RESULTS: C-allele of insulin -2221 MspI and G-allele of +49 CTLA-4 were significant risk factors for type 1 diabetes (crude OR 3.53 and 1.59, respectively) and this impact increased in the homozygous form of both alleles. The regression model supported the idea of insulin CC and CTLA-4 GG genotypes for an independent and clearly significant risk for developing type 1 diabetes. We could not detect any significant correlation between investigated polymorphisms and type 2 diabetes. CONCLUSIONS: There exists a significant association between the C-allele of -2221 MspI in the insulin gene and type 1 diabetes. The CTLA-4 G-allele is also positively correlated with type 1 diabetes. According to the regression model the investigated gene polymorphisms are independent risk factors for development of type 1 diabetes in the Estonian population. We propose that -2221 MspI is a good marker for evaluation of risk of insulin gene haplotype in type 1 diabetes patients.     

中国人群let-7基因rs10877887多态性与癌症风险相关性的Meta分析

目的评价中国人群let-7基因rs10877887多态性与癌症风险之间的相关性。方法通过检索PubMed、Embase、万方数据库中的相关文献(检索日期截止到2016年12月31日),共纳入4个符合标准的病例-对照研究,包含2 754例病例和3 481例对照。采用优势比(OR)和95%可信区间(95%CI)进行let-7基因rs10877887多态性与癌症风险之间的相关性评价,同时也对敏感性和发表偏倚进行分析。结果 Meta分析结果表明,在Dominant模型(CC+CTvs.TT)下,let-7基因rs10877887多态性与癌症风险之间存在显著相关性(CC+CT vs.TT:OR=0.90,95%CI=0.82~1.00,P=0.048),可降低癌症发生的总体风险。结论基于目前研究的Meta分析结果表明,中国人群中let-7基因rs10877887多态性与癌症风险具有显著相关性,可降低癌症发生的总体风险。     

The IL-17A rs2275913 polymorphism is associated with colorectal cancer risk

ObjectiveThe association of the IL-17A rs2275913 polymorphism with the risk of colorectal cancer (CRC) has been previously reported. However, the results are inconsistent. In this study, we comprehensively assessed the effect of the rs2275913 polymorphism on CRC risk.MethodsThe rs2275913 polymorphism of 208 CRC patients and 312 age- and gender-matched healthy controls was genotyped by the polymerase chain reaction-restriction fragment length polymorphism method, and then analyzed by logistic regression. In addition, a pooled analysis based on five single-center studies was performed using Stata 12.0 software.ResultsLogistic regression analysis indicated that the IL-17A rs2275913 polymorphism was associated with CRC risk (GA vs. GG: OR = 1.53, 95% CI = 1.02–2.28; AA vs. GG: OR = 1.89, 95% CI = 1.11–3.20; GA+AA vs. GG: OR = 1.62, 95% CI = 1.11–2.37; A vs. G: OR = 1.38, 95% CI = 1.07–1.77). Further pooled analysis also indicated a statistically significant association between the rs2275913 polymorphism and CRC risk in Asians and Northern Africans.ConclusionThis study suggested that the IL-17A rs2275913 polymorphism may act as a biomarker for predicting CRC risk. However, further functional research should be performed to clarify the role of the rs2275913 polymorphism in the etiology of CRC.