细胞毒T淋巴细胞相关抗原4基因多态性与溃疡性结肠炎

目的炎症性肠病的发病与T细胞过度活化有关,细胞毒T淋巴细胞相关抗原4（CTLA-4）是重要的T细胞活化负性调节因子.本课题研究CTLA-4基因启动子区-1722位点（T/C）及-1661位点（A/G）多态性与中国汉族人群中溃疡性结肠炎（UC）的相关性.方法采用PCR-限制性片段长度多态性方法,对87例中国汉族UC患者和116例正常对照者进行CTLA-4基因-1722位点和-1661位点多态性检测.结果UC患者CTLA-4基因-1661位点A/G＋G/G基因型频率,-1661位点G等位基因频率显著高于正常对照组（34.5%比15.5%,P=0.002,OR=2.865,95%CI=1.467～5.596;19.0%比8.2%,P=0.002,OR=2.624,95%CI=1.435～4.796）;而在-1722位点的基因型频率、等位基因频率与对照组比较差异无统计学意义（P＞0.05）.结论CTLA-4基因启动子区-1661位点G等位基因与中国汉族UC存在显著相关性.     

细胞毒性T淋巴细胞相关抗原4基因微卫星多态性与炎症性肠病的关系

目的探讨细胞毒性T淋巴细胞相关抗原4（CTLA-4）基因微卫星多态性与浙江省炎症性肠病（IBD）患者的相关性。方法对118例无血缘关系的IBD患者（99例溃疡性结肠炎，19例克罗恩病）以及140例正常对照者，采用特异性等位基因PCR方法，检测CTLA-4外显子4的3′非翻译区包含（AT）。重复序列的等位基因。扩增产物用12％非变性聚丙烯酰胺凝胶电泳，硝酸银染色。结果CTLA-4微卫星共有20种等位基因。与正常对照组比较，122bp等位基因频率在溃疡性结肠炎患者（P=0.0001／Pc=0．0025，OR=11.393，95％CI：2．574～50．429）和克罗恩病患者（P=0．0003／Pc=0.0050，OR=21.061，95％CI：3，927～112．94）中均显著增高。结论CTLA-4基因微卫星多态性与浙江省IBD患者显著相关。     

Graves眼病与细胞毒性T淋巴细胞相关抗原4基因启动子和外显子1多态性的相关性研究

Gmves病(GD)为一常见的内分泌疾病，其临床表现常不局限于甲状腺，而表现为多器官受损，眼是常受累器官之一。有证据显示，Graves眼病(GO)的发病具有遗传倾向。由于遗传易感基因受种族和环境的影响，所以目前尚无一种遗传学标志能够准确地预测GD的发生，而细胞毒性T淋巴细胞相关抗原4(CTLA-4)基因是主要的候选致病基因之一。     

细胞毒T淋巴细胞相关抗原4基因多态性与汉族溃疡性结肠炎患者的相关性研究

目的　研究细胞毒T淋巴细胞相关抗原4(CTLA- 4)基因外显子1的49位点A/G和启动子- 318位点C/T多态性与溃疡性结肠炎(UC)的相关性。方法　采用序列特异性引物聚合酶链反应(PCR -SSP)方法,检测82例中国湖北汉族溃疡性结肠炎患者(UC)以及204 例健康对照者CTLA- 4 基因外显子1的49位点A/G和启动子-318位点C/T的基因型和单倍型。结果　UC患者CTLA -4 A+49G和C- 318T基因型与正常对照组间差异无统计学意义(P>0.05),且与性别无关。在单倍型分析中,UC患者CTLA -4单倍型2,3(C-318 G49/T-318 A49)显著低于正常人群(26%比41%,P<0.05,OR=0.4918,95%CI:0.2784~0.8688)。结论　UC患者CTLA- 4 基因A+49G和C -318T单倍型2,3 与UC呈负相关。     

细胞毒性T淋巴细胞相关抗原4 CT60及JO31基因多态性与炎症性肠病的相关性

炎症性肠病（IBD）是一种慢性肠道非特异性炎症,主要包括溃疡性结肠炎（UC）和克罗恩病（CD）,其病因及发病机制多认为是包括感染在内的环境因素作用于具有遗传易感性的个体,诱发异常免疫反应而导致疾病.     

细胞毒性T淋巴细胞相关抗原4基因多态性与炎症性肠病的相关性

目的 炎症性肠病(IBD)的发病机制与T细胞免疫应答过度有关。细胞毒T淋巴细胞相关抗原4(CTLA-4)主要在已激活的T细胞上表达,通过与CD28竞争与B7结合,抑制T细胞激活,维持免疫系统内环境稳定。CTLA-4基因多态性与一些自身免疫性疾病相关,但未见其与IBD的研究。本研究旨在了解IBD的遗传易感性。方法 对68例无血缘关系的湖北汉族IBD患者(54例溃疡性结肠炎,14例克罗恩病)以及140例正常对照者,采用序列特异性引物PCR方法检测CTLA-4外显子4的3’非转录区包含AT重复序列的特异性等位基因。扩增产物用12％非变性聚丙烯酰胺凝胶电泳,硝酸银染色,部分样品经测序以确定片段长度。结果 共发现CTLA4基因有18种等位基因,与正常对照组比较,122bp等位基因在溃疡性结肠炎患者中显著增高(7．4％vs0．3％,P=0．0002／Pc=Sig,OR=22．32．95％CI：2．76～180．80)。结论 CTLA-4基因微卫星多态性与溃疡性结肠炎显著相关。     

细胞毒性T淋巴细胞相关抗原-4+49基因多态性与自身免疫性肝病相关

自身免疫性肝炎(autoimmune hepatitis，AIH)和原发性胆汁性肝硬化(primary biliary cirrhosis,PBC)是两组重要的自身免疫性肝病，多基因遗传因素在AIH和PBC的发生发展中起重要作用。细胞毒性T淋巴细胞相关抗原-4(CTLA-4)基因位于染色体2q33区域，其外显子1区基因多态性与高加索人种的AIH和PBC相关。我们采用限制性片段长度多态性分析法(PCR-RFLP)分析了49例AIH和58例PBC患者CTLA-4外显子1区49位A／G单核苷酸多态性，并与正常献血者作比较。     

炎症性肠病患者外周血单个核细胞细胞毒性 T淋巴细胞相关抗原4的表达

背景:细胞毒性T淋巴细胞相关抗原(CTLA)4是一种重要的免疫细胞共刺激分子,主要表达于活化的T淋巴细胞,对T细胞的激活起抑制作用。目的:通过检测炎症性肠病(IBD)患者外周血单个核细胞表面CTLA4的表达,探讨CTLA4在IBD发病中的作用和功能。方法:将18例活动性溃疡性结肠炎(UC)、4例活动性克罗恩病(CD)患者以及21名健康对照者外周血单个核细胞分离后,以流式细胞仪检测细胞表面CTLA4、CD4 和CD8 的表达。结果:自然状态下,UC和CD患者CD4 CTLA4 表达显著高于对照组(8.2%±4.7%对1.4%±1.3%,P<0.001;4.3%±2.9%对1.4%±1.3%,P=0.011);CD8 CTLA4 表达亦显著高于对照组(9.1%±7.2%对0.9%±0.3%;8.7%±3.5%对0.9%±0.3%,P均<0.001)。经植物血凝素(PHA)刺激后,IBD患者和对照组外周血单个核细胞CTLA4的表达均增加;CD组CD8 CTLA4 表达显著高于对照组(35.0%±10.9%对18.1%±10.1%,P=0.005)。结论:活动性UC和CD患者外周血单个核细胞CTLA4表达增强,提示T细胞激活第二信号通路B7/CD28/CTLA4在IBD的发病过程中起重要作用。     

细胞毒性T淋巴细胞相关抗原4基因多态性与中国汉族人1型糖尿病、自身免疫性甲状腺病的相关性研究

目的 探讨细胞毒性T淋巴细胞相关抗原4（CTLA－4）基因外显子1的49位点A／G多态性与中国汉族人1型糖尿病、自身免疫性甲状腺病（AITDs）的关系。方法 对33例典型1型糖尿病患者、57例成人晚发自身免疫性糖尿病患者（LADA）、122例自身免疫甲状腺疾病患者（AITDs）和84例健康对照者采用聚合酶链反应－限制性片段长度多态性（PCR－RFLP）技术分析CTLA－4基因外显子1的49位点基因型。结果 1型糖尿病患者的CTLA－4G等位基因频率显著高于对照组（P＝0．0005）;胰岛细胞抗体和谷氨酸脱酶脱羧酶抗体阳性率与G无明显相关性。AITDs患者CTLA－4G等位基因频率高于对照组（P＜0．0001）;Graves病组按性别分层分析后发现G等位基因在不同性别的分布差异无显著性。12例AITDs患者同时合并糖尿病,其CTLA－4G等位基因频率与单纯AITDs患者相比差异无显著性。结论 CTLA－4基因外显子1多态性与中国汉族人1型糖尿病、AITDs有关,G等位基因是1型糖尿病、AITDs的危险因素之一。     

原发性胆汁性胆管炎患者血浆细胞毒性T淋巴细胞相关蛋白4基因多态性分析

目的 探讨原发性胆汁性胆管炎(PBC)患者血浆细胞毒性T淋巴细胞相关蛋白4(CTLA-4)基因多态性变化。方法 2015年9月～2020年12月我院诊治的PBC患者30例和同期健康体检者35例,采用聚合酶链反应-限制性片段长度多态性检测血浆CTLA－4基因rs231775、 rs4675369和rs7599230位点多态性。Logistic回归分析疾病风险关联。结果 PBC患者CTLA－4基因rs7599230位点基因型为CC型、CT型和TT型比率分别为16.7%、46.7%和36.6%,与健康人的20.0%、45.7%和34.3%比,无显著性差异(P＞0.05),等位基因C和T比率分别为40.0%和60.0%,与健康人群的42.9%和57.1%比,也无显著性差异(P＞0.05);PBC患者CTLA－4基因rs231775位点基因型为GG型和等位基因G比率分别为40.0%和61.7%,显著高于健康人的14.2%和35.7%(P＜0.05),AA基因型和等位基因A比率分别为16.7%和38.3%,显著低于健康人的42.9%和64.3%(P＜0.05);PBC患者CTLA－4基因rs4675369位点基因型为GG型和等位基因G比率分别为43.3%和65.0%,显著高于健康人的17.1%和41.4%(P＜0.05),AA基因型和等位基因A比率分别为13.4%和35.0%,显著低于健康人的34.3%和58.6%(P＜0.05);经非条件Logistic回归模型计算,校正性别和年龄,结果显示rs4675369位点GG基因型是影响PBC发生的危险基因型,其OR值为1.523((95%CI:1.113～2.085),rs231775位点GG基因型也是影响PBC发生的危险基因型,其OR值为1.636((95%CI:1.161～2.305) 。结论 CTLA-4基因rs231775和rs4675369位点GG基因型可能是PBC发生的易感基因型,值得进一步研究。     

CTLA-4基因多态性与中国南方汉族人Graves病的相关性

用PCR-RFLP和PCR．SSLP分别确定CTLA-4基因第1外显子49位点基因型和第4外显子3，末端AT重复序列的基因型，分析广东汉族120例Graves病患者及123名正常对照组CTLA-4基因多态性。结果显示CTLA-4基因外显子1A49G及外显子4（AT）n多态性与广东汉族人GD不相关。     

染色体2q31-q33区CTLA-4基因多态性与格雷夫斯病关系的研究

目的探讨位于2号染色体长臂3区1～3带(2q31-q33)的细胞毒性T淋巴细胞相关抗原-4(cytotoxicTlymphocyteassociatedantigen4,CTLA-4)基因多态性与格雷夫斯病(Gravesdisease,GD)的关系。方法应用聚合酶链反应-单链长度多态性分析的方法(PCR-SSLP)确定细胞毒性T淋巴细胞相关抗原-4(CTLA-4)基因第4外显子3′末端AT重复序列的基因型,分析2001-03～2003-03收集在中山大学附属第一医院广东地区汉族人120例GD患者及123名正常对照组CTLA-4基因多态性。结果CTLA-4基因3′末端微卫星位点有20个等位基因,两组之间的基因频率差异无统计学意义(P>0.05)。结论定位于染色体2q31-q33区CTLA-4基因可能不是中国广东地区汉族人GD的主要易感基因。     

Analysis of cytotoxic T lymphocyte associated antigen 4 gene polymorphisms in patients with ulcerative colitis

BACKGROUND AND AIM: Ulcerative colitis (UC) is a multifactorial disease associated with dysregulated immunity. Recently, cytotoxic T lymphocyte associated antigen 4 (CTLA-4) gene polymorphisms have been reported in association with several autoimmune diseases in several populations. In the present study, the possible implication of the CTLA-4 gene as a risk factor for UC in the Iranian population was investigated. METHODS: One hundred UC patients and 100 healthy subjects were studied. CTLA-4 exon 1 position 49 (A/G: codon 17: Thr/Ala) polymorphisms were investigated by polymerase chain reaction single strand confirmation polymorphism method. Four of the patients and one of the healthy controls were excluded from the study because of incomplete DNA extraction. RESULTS: The allele frequencies of A and G in 96 patients (A: 66.1%; G: 33.9%) were not significantly different from the 99 control subjects (A: 63.1%; G: 36.9%, P > 0.05). No significant differences in the distribution of genotype frequencies were observed between A + 49G gene polymorphisms and UC in the Iranian population (P > 0.05). CONCLUSION: CTLA-4 polymorphism is not associated with UC in the Iranian population.     

No association of the cytotoxic T-lymphocyte associated gene CTLA4 ＋49A/G polymorphisms with Crohn＇s disease and ulcerative colitis in Hungarian population samples

AIM： The goal of the current work was to analyse the prevalence of the ＋49A/G variant of the cytotoxic T-lymphocyte antigen 4 gene （CTLA4） in Hungarian patients with Crohn＇s disease （CD） and ulcerative colitis （UC）.
METHODS： A total of 130 unrelated subjects with CD and 150 with UC, and 170 matched controls were genotyped for the single nucleotide polymorphism （SNP）. The genotypes were determined by using PCR/RFLP test.
RESULTS： The G allele frequency and the prevalence of the GG genotype were 38.1% and 12.3% in the CD group, 40.6% and 18.6% in the UC patients, and 37.4% and 15.9% in the control group, respectively.
CONCLUSION： The results of the current study show that carriage of the ＋49G SNP in heterozygous or in homozygous form does not confer risk either for CD or for UC in the Hungarian population.     

Association of cytotoxic T lymphocyte associated antigen-4 gene (rs60872763) polymorphism with Crohn's disease and high levels of serum sCTLA-4 in Crohn's disease

Background and Aim: Our aim was to evaluate cytotoxic T lymphocyte associated antigen‐4 (CTLA‐4) gene polymorphisms in Crohn's disease (CD) and explore soluble CTLA‐4 (sCTLA‐4) levels in serum of CD patients in central China. Methods: A total of 126 Chinese CD patients and 300 healthy controls were enrolled in this study. CTLA‐4 (AT)n repeat polymorphism was genotyped by a semiautomatic fluorescently labeled polymerase chain reaction (PCR) method, and CTLA‐4 ‐1661A/G and ‐1722T/C polymorphisms were genotyped by DNA sequencing. Serum sCTLA‐4 and C‐reactive protein (CRP) levels were determined by enzyme linked immunosorbent assay (ELISA) and immunonephelometry, respectively. Results: The frequency of 84 bp allele of CTLA‐4 (AT)n repeats was lower in CD patients than in the healthy controls (22.2% vs 33.2%, P = 0.001, odds ratio = 0.58, 95% confidence interval: 0.41–0.81). The 84 bp allele carriers of (AT)n repeats were associated with non‐stricturing and non‐penetrating disease behavior in CD patients (P = 0.007). Serum sCTLA‐4 levels were more elevated in CD patients than in the healthy controls (P < 0.001). Among CD patients, serum sCTLA‐4 levels were increased in active disease compared with inactive disease (P = 0.015), and were correlated with CRP levels (r = 0.524, P < 0.001). Serum sCTLA‐4 levels were higher in CD patients with stricturing disease behavior than in patients with other disease behaviors (P = 0.009). Conclusions: 84 bp allele of CTLA‐4 (AT)n repeat polymorphism was associated with CD in central China. sCTLA‐4 levels were highly expressed in CD, especially in active disease, and were correlated with CRP levels and disease behavior in CD patients.