CTLA-4基因多态性与粤西汉族人Graves病遗传易感性的关系

应用限制性片段长度多态性方法检测102例Graves病(Graves'disease,GD)及伴Graves眼病(Graves'ophthalmopathy,GO)亚组患者与100例正常组细胞毒性T淋巴细胞相关抗原-4(cytotoxic T lymphocyte associated antigen-4,CTLA-4)基因外显子1+49位点A/G及启动子-318位点C/T多态性。以探讨CTLA-4基因外显子1+49位点和启动子-318位点多态性与粤西汉族人GD及GO发病的关联性。结果显示GD组外显子1+49位点的GG基因型及G等位基因频率显著高于正常组(P=0.0142、0.0017),GD组AA基因型及A等位基因频率显著低于正常组(P=0.0079、P=0.006);启动子-318位点的各基因型及等位基因频率与正常组相比无统计学意义;外显子1+49位点和启动子-318位点基因型、等位基因频率在GO、无眼病GD亚组及正常组中任两组比较均无统计学意义。研究提示CTLA-4基因外显子1+49位点GG基因型及G等位基因可能是粤西汉族人GD的易感因素,但与GO无相关,AA基因型及A等位基因则是保护因素;启动子-318位点多态性与粤西汉族人GD及GO均不相关。     

CTLA-4基因多态性与特发性扩张型心肌病的相关性

目的包括细胞和体液免疫在内的自身免疫机制至少参与了部分特发性扩张型心肌病(Idiopathicdilatedcar-diomyopathy,IDC)患者的发病,且前者介导的心肌损害在IDC中更重要。CTLA-4是特异性细胞免疫的负性调节因子。本研究旨在探讨CTLA-4基因启动子-318C/T、外显子A/G多态性及3′非翻译区(AT)n微卫星多态性与IDC及血清可溶性CT-LA-4(sCTLA-4)水平的相关性。方法采用聚合酶链反应-限制性片段长度多态性(Polymerasechainreaction-restrictionfragmentlengthpolymorphisms,PCR-RFLP)方法分析黑龙江省无血缘关系汉族人群(包括72例IDC患者,100例正常健康人)CTLA-4基因-318C/T、49位点A/G多态性及3′微卫星多态性;ELISA法检测血清sCTLA-4水平。综合分析CTLA-4基因型频率、等位基因频率与IDC及sCTLA-4水平的相关性。结果IDC组外显子1GG基因型和G等位基因频率显著高于正常对照组(P=0.012,P=0.008);3′非翻译区共发现18种等位基因,106bp等位基因频率在IDC患者中显著增高(22.22%vs1%,P=0.0002,OR=23.56,95%CI9.65~83.74);两组间-318C/T多态性分布无统计学差异。与对照组相比,IDC组sCTLA-4水平显著升高[(1.87±1.06)μg/L比(0.54±0.19)μg/L,P<0.05];直线回归分析显示,IDC组GG基因型及G等位基因频率与血清sCTLA-4水平(r=0.57,P=0.021)显著相关,而AA、A/G基因型及A等位基因频率与sCTLA-4水平无相关性。启动子-318C/T多态性及3′非翻译区(AT)n微卫星多态性与sCTLA-4水平的亦无相关性。结论CTLA-4基因外显子1A49→G变异与IDC相关,携带G等位基因者易患IDC,其机制可能为该多态性造成CTLA-4信号肽中编码苏氨酸和甘氨酸的替换,从而影响蛋白翻译后加工、修饰,使sCTLA-4功能发生变化。提示3′末端非翻译区(AT)n重复序列中106bp等位基因可能是IDC的易感基因。     

CTLA-4基因多态性在重症肌无力发病机理中的作用

目的探讨细胞毒性T淋巴细胞相关抗原-4(cytotoxicTlymphocyteassociatedantigen-4,CTLA-4)基因第1外显子 49位点、启动区-318、-1661、-1772位点的多态性及其导致的无效转录对重症肌无力(myastheniagravis,MG)遗传易感性的影响。方法酶联免疫吸附实验测定MG患者和健康对照血清中可溶性CTLA-4的水平;限制性片段长度多态性分析检测第1外显子 49位点、启动区-318、-1661、-1772位点的多态性;转录因子核因子(nuclearfactor1,NF-1)和CCAAT/增强子结合蛋白β(CCAAT/enhancerbindingproteinbeta,c/EBPβ)结合位点通过染色质免疫沉淀实验得以验证。结果启动区-1772、-1661位点和第1外显子 49位点的多态性与MG,特别是伴发有胸腺瘤的MG密切相关。启动子-318位点的多态性与MG无关。CTLA-4基因4个多态性位点间有一个明确的正性连锁不平衡关系。MG患者血清可溶性CTLA-4的表达水平与等位基因的突变相关联。-1772、-1661位点的多态性可改变转录因子NF-1和c/EBPβ结合位点,而ConA、PHA则能促进NF-1和c/EBPβ的这种位点特异性转录活性。结论MG患者CTLA-4A/G 49、C/T-1772和A/G-1661多态性可导致无效转录,影响MG的遗传易感性,T→C-1772的突变能影响基因的剪接,从而干扰蛋白的表达和功能。     

甘露糖结合凝集素与儿童常见感染易感性的关系研究

目的 研究浙江省汉族儿童中甘露糖结合凝集素(MBL)基因多态性和蛋白水平与常见感染(反复呼吸道感染、急性呼吸道感染、CMV活动性感染、体表局部脓肿、中耳炎)易感性的关系.方法 用PCR和测序法对感染组和对照组儿童的MBL基因启动子区和外显子1区的6个突变位点进行检测和分型,用ELISA试剂盒检测两组儿童的血浆MBL蛋白浓度.结果 感染组和对照组均未检测到MBL基因外显子1区+223位点(C/T)和+239位点(G/A)的突变,对照组也未检测到启动子区+4位点(C/T)的突变.启动子区-550位点3种基因型HH、HL、LL在感染组和对照组的频率分别为43.1％、29.1％、27.8％和63.8％、17.1％、19.1％,两组间基因型频率差异有统计学意义(P＜0.05).启动子区和外显子1区所有基因型组合形成的完整基因型可分为与血浆蛋白浓度相关的“YA型”和“XB型”,两种完整基因型频率在感染组和对照组间差异有统计学意义(P＜0.05).感染组和对照组血浆MBL蛋白浓度均呈偏态分布.CMV感染组蛋白浓度低于对照组,急性呼吸道感染和局部脓肿组蛋白浓度高于对照组,差异均有统计学意义(P＜0.05).结论 包括启动子区和外显子1区在内的MBL基因多态性与儿童常见感染的易感性具有一定相关性.     

白细胞介素10基因启动子区多态性与乙型肝炎病毒感染预后的关联研究

目的探讨中国汉族人白细胞介素10基因(interleukin10gene,IL10)启动子区单核苷酸多态性与乙型肝炎病毒(hepatitisBvirus,HBV)感染、转归的关联。方法采用聚合酶链反应-限制性片段长度多态性分析方法,检测231例HBV感染者,165例HBV感染康复者和135名正常对照者IL10基因启动子-1082G/A、-819T/C、-592A/C位点基因型。结果IL10基因启动子-1082G/A、-819T/C、-592A/C位点基因型和等位基因在HBV感染组、HBV感染康复组和正常对照组之间的分布频率比较差异无统计学意义(P>0.05),在血清HBV-DNA<1×103拷贝/mL的HBV感染者组和HBV-DNA≥1×103拷贝/mL组之间的分布频率比较差异亦无统计学意义(P>0.05);但IL10基因启动子-819T/C和-592A/C位点基因型和等位基因在HBV无症状携带组和慢性乙型肝炎组之间的分布差异有统计学意义(P<0.05),-819T/C位点TT型和-592A/C位点AA型在慢性乙型肝炎组的频率明显较高。结论汉族人IL10基因启动子多态性可能与人群对HBV易感性及感染后的病毒血症水平无显著相关性;但IL10启动子-819T/C和-592A/C位点基因多态性与HBV感染后的肝脏炎症反应有关。     

FcRL3基因三个单核苷酸多态性与重庆汉族人群Graves病关联研究

目的 了解中国重庆地区汉族人群Fc受体样因子(Fc receptor-like proteins,FcRL3)基因启动子A/G,第2外显子C/G,第4外显子C/T多态性与Graves病(Graves disease,GD)的相关性.方法 采用聚合酶链反应限制性片段长度多态性分析方法结合直接测序技术,对重庆地区无亲缘关系的120名正常人和128例GD患者进行多态性研究,同时进行甲状腺功能和自身抗体的检测,应用Unphased1122和LDA1.0软件进行连锁不平衡和单倍型分析,用卡方检验分析基因型、等位基因和单倍型频率在GD组和对照组之间的差异.结果 GD组FcRL3基因3个多态性位点基因型和等位基因的频率与对照组相比,其差异均有统计学意义(P＜0.05).连锁不平衡分析显示启动子和第2外显子存在连锁不平衡,在构建的3个主要单倍型中,仅H2(G-G)单倍型频率GD组明显高于对照组(50.8%vs 35.8%,P＜0.05).除甲状腺疾病家族史与启动子多态性有关联(P%0.05),余临床特征与FcRL3多态性均无相关.结论 多个位点及单倍型分析提示FcRL3基因启动子A/G,第2外显子C/G,第4外显子C/T多态性可能是中国重庆地区汉族人群GD关联的危险因素.     

细胞毒T淋巴细胞相关抗原4基因C-658T多态性与溃疡性结肠炎相关性研究

,与UC患者的病变范围有显著相关(P=0.037;P=0.0067);UC组C61T基因型频率与对照组相比,差异无统计学意义(P=0.192).结论 CTLA-4基因启动子区C-658T位点T等位基因与中国汉族UC存在显著相关性.     

SLC22A12基因第8外显子和第8内含子多态与中国汉族人原发性高尿酸血症关联研究

目的 研究原发性高尿酸血症患者SLC22AI2基因第8内含子和第8外显子单核苷酸多态(single nucleotide polymorphism,SNP)位点与原发性高尿酸血症遗传易感性的关系.方法 选择山东沿海地区原发性高尿酸血症患者215例,正常对照人群323名.提取基因组DNA,PCR扩增SLC22A12基因第8内含子和第8外显子,对PCR扩增产物进行测序.结果 序列分析发现:(1)SLC22AI2基因第8外显子存在T1309C单核苷酸多态,第8内含子存在-103A＞G单核苷酸多态,这2个多态位点完全连锁.(2)高尿酸血症组-103A＞G G等位基因频率和T1309C C等位基因频率明显高于正常对照组(均为51.9%vs.42.4%,P＜0.01);(3)高尿酸血症组GG+GA基因型频率和CC+CT基因型频率显著高于正常对照组(均为80.0%vs.69.0%,P＜0.01).(4)-103 A＞G和T1309C基因多态中,含有等位基因G的基因型GG+GA及含有等位基因C的基因型CC+CT均使高尿酸血症的发病危险性上升了1.79倍(OR=1.79,95%CI:1.19～2.70).结论 SLC22A12基因第8外显子T130gC及第8内含子-103A＞G SNP与原发性高尿酸血症密切相关.     

IL-10基因启动子多态性与皖南地区汉族人群支气管哮喘的相关性研究

目的:探讨IL-10基因启动子-1082G/A(rs1800896)、-819C/T(rs1800871)、-592C/A(rs1800872)位点多态性与安徽皖南地区汉族人群支气管哮喘的相关性。方法:采用病例-对照方法,用聚合酶链反应及直接基因测序法比较183例支气管哮喘组与151例正常人对照组之间基因型、等位基因频率的差异。结果:哮喘组IL-10基因启动子-1082G/A、-592C/A位点基因型与对照组相比有差异(P<0.05),其等位基因型频率在哮喘组和对照组间亦有差异(P<0.05)。而-819C/T位点基因型及等位基因型频率在哮喘组和对照组间均无差异(P>0.05)。结论:IL-10基因启动子rs1800896(-1082G/A)位点和rs1800872(-592C/A)位点的多态性可能与安徽皖南地区汉族哮喘相关;而rs1800871(-819C/T)位点的多态性可能与安徽皖南地区汉族哮喘无相关。     

PTPN22基因多态性与自身免疫甲状腺病的相关性

目的:检测PTPN22基因的单核苷酸多态性(SNP)及其与中国人自身免疫甲状腺病(AITD)的相关性, 并研究CTLA- 4基因SNP与PTPN22 SNP的相互关系.方法:采用PCR-RFLP技术分析231例AITD患者, 其中Graves'病(GD)149例, 桥本甲状腺炎(HT)82例和131例健康对照者PTPN22基因 1858 C>T及CTLA- 4基因49A>G位点的基因型.采用SASP-PCR技术分析PTPN22基因启动子-1123G>C的基因型.结果:(1)PTPN22基因的 1858C>T位点不存在多态性;(2)PTPN22基因-1123G>C SNP的等位基因和基因型分布频率在GD组与正常对照组间的差异有统计学意义(P值分别为0.040和0.013, OR值分别为1.44和2.33);(3) CTLA- 4基因 49A>G位点的等位基因和基因型分布频率在AITD组与正常组间有明显差异;(4)与携带PTPN22的G等位基因及CTLA- 4的AA基因型者相比, 携带PTPN22CC基因型与CTLA- 4 AG或GG基因型者发生GD的OR值=3.31(95%CI: 2.69-8.89).结论:PTPN22基因启动子-1123G>C SNP与GD的发生相关, 其CC基因型与CTLA- 4基因的G 等位基因对GD的发生起协同作用.     

Lack of association between CD28/CTLA-4 gene polymorphisms and atopic asthma in the Japanese population

Atopic asthma occurs in genetically susceptible individuals in the presence of environmental factors. Recently, the costimulation signal from CD80-CD86 to CD28/CTLA-4 has been suggested to play an important role in the development of atopic asthma. In the present study, we analyzed three polymorphic regions within the CTLA-4 gene, an A/G substitution in exon 1 position 49, a C/T base exchange in the promoter position -318 and an (AT)n repeat polymorphism in the 3'-untranslated region of exon 4, and a CD28 gene polymorphism with a T/C substitution in intron 3 position +17 in 120 patients with atopic asthma and 200 normal controls. The polymorphism frequencies of CTLA-4/CD28 genes in patients did not differ from those in normal controls. Thus, the present study was unable to reveal any association between CTLA-4/CD28 gene polymorphisms and atopic asthma in the Japanese population.     

CTLA-4 +49 A/G and −318 C/T polymorphisms and susceptibility to multiple sclerosis: a meta-analysis

Objective: The aim of this study was to explore whether cytotoxic T lymphocyte antigen-4 (CTLA-4) +49 A/G, and ?318?C/T polymorphisms confer susceptibility to multiple sclerosis (MS).

Methods: A meta-analysis of the associations between the CTLA-4 +49?A/G and ?318?C/T polymorphisms and MS.

Results: A total of 23 separate comparisons from 19 studies of the CTLA-4 +49 A/G polymorphism and 10 comparisons (8 studies) of the CTLA-4 ?318?C/T polymorphism were considered. Meta-analysis showed no association between MS and the CTLA-4 +49G allele in the analysis of all study subjects (OR?=?1.026, 95% CI?=?0.967–1.089, p?=?0.395). Stratification by ethnicity indicated no association between the CTLA-4 +49G allele and MS in Caucasians, Asians, or Arabs. Meta-analysis showed no association between RA and the CTLA-4 ?318C allele in all study subjects (OR?=?0.909, 95% CI?=?0.704–1.175, p?=?0.467). In addition, meta-analysis stratified by ethnicity revealed no association between MS and the CTLA-4 ?318 C/T polymorphism in Caucasian, Asian, or Arab populations.

Conclusions: This meta-analysis of published studies did not find an association between the CTLA-4 +49?A/G and ?318?C/T polymorphisms and susceptibility to MS in Caucasian, Asian, and Arab populations.     

中国人自身免疫性肝病相关性 CTLA-4基因多态性研究

目的　探讨细胞毒性 T细胞相关抗原 - 4 (cytotoxic T lymphocyte- associated antigen- 4 ,CTL A- 4 )基因启动子 - 318和第 1外显子区第 4 9位基因多态性与中国人自身免疫性肝炎 (autoimmunehepatitis,AIH)、原发性胆汁性肝硬化 (primary biliary cirrhosis,PBC)发病的相关性。方法　应用限制性片段长度多态性方法分析 6 2例 AIH和 77例 PBC患者外周血单核细胞基因组 DNA CTL A- 4启动子 -318T/ C、第 1外显子区第 4 9位基因 A/ G多态性 ,并与 16 0名正常对照比较。结果　 AIH组 CTL A- 4启动子 - 318位 T/ C基因型分布与对照组比较差异无显著性 ,但 C等位基因频率明显高于正常对照组 (P=0 .0 2 ,OR=2 .4 3)。 PBC患者 CTL A- 4第 1外显子区第 4 9等位基因分布与正常对照组比较差异非常显著(P=0 .0 0 6 ) ,PBC患者 G等位基因频率明显高于正常组 (P=0 .0 0 4 6 ,OR=1.8)。联合分析 CTL A- 4启动子与第 1外显子的基因多态性分布 ,虽然 AIH组和 PBC组 GG- CC型携带率均比正常人高 (AIH组 :32 .3% ,PBC组 :37.7% ,对照组 :2 2 .5 % ) ,但是统计学分析结果均显示两组患者与正常人差异无显著性。结论　 CTL A- 4启动子 - 318和第 1外显子区第 4 9位基因多态性可能与中国人 AIH、PBC易感性相关。     

Association of -318 C/T and +49 A/G cytotoxic T lymphocyte antigen-4 (CTLA-4) gene polymorphisms with a clinical subset of Italian patients with systemic sclerosis

Systemic sclerosis (SSc) is a complex and heterogeneous autoimmune disorder with a multi-factorial pathogenesis. Like other autoimmune disorders, the possible role of specific cytotoxic T lymphocyte antigen-4 (CTLA-4) gene polymorphisms in predisposing to SSc has been hypothesized, but it remains controversial. CTLA-4 promoter (-318C/T) and exon 1 (+49 A/G) polymorphisms have been analysed in 43 Italian females with SSc and in 93 unrelated matched healthy controls by a newly designed tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) method. No significant association has been found with either polymorphisms.Nevertheless, SSc patients without concomitant Hashimoto's thyroiditis (HT) were carrying both the -318T allele (P = 0.031) and the +49 G allele (P = 0.076) more frequently than SSc patients with HT [defined by positivity for anti-thyroperoxidase (TPO) and anti-thyroglobulin (TGA) autoantibodies] than controls. Haplotype analysis confirms this association (P = 0.028), and suggests the predominant role of the -318T, whereas that of the +49 G, if any, seems weak. Thus, in Italian SSc patients the CTLA-4 -318C/T promoter polymorphism appears to be associated with the susceptibility to develop SSc without thyroid involvement. Larger studies are needed to confirm these findings and to clarify whether the -318C/T polymorphism is the functional responsible or whether it reflects the presence of another linked genetic element in the same chromosomal region.     

Association of CTLA-4 and CD28 Gene Polymorphisms with Type 1 Diabetes in South Indian Population

Each functional gene illustrates the complexity of genetic predisposition to disease; however, it is difficult to bring out these traits with reference to autoimmune diseases like type 1 diabetes (T1D). To find out the genetic contribution of CTLA-4 + 49A/G, CTLA-4 ?318C/T and CD28 + 17T/C polymorphisms toward T1D, the present study was performed with 124 T1D patients, 54 siblings and 125 parents including 39 trios in South Indian population. The association and linkage of CTLA-4 + 49A/G, CTLA-4 ?318C/T and CD28 + 17T/C polymorphisms with T1D were analyzed and transmission disequilibrium test was performed. CTLA-4 G allele carrying genotypes (GG+AG) showed a higher risk association and can be considered as susceptible to develop T1D among patients with age at diagnosis from 0 to 10 years as compared to siblings (OR = 2.9; p_c = 0.047) and parents (OR = 2.7; p_c = 0.036). On the other hand, a strong protection against the disease (age at diagnosis; 0–10 years) was observed with CTLA-4 + 49AA genotype (OR = 0.37; p_c = 0.036) and combined AA/CC genotype (OR = 0.31; p_c = 0.034) of CTLA-4 + 49A/G and CTLA-4 ?318C/T polymorphisms. However, a significant association was not observed between CTLA-4 ?318C/T and CD28 + 17T/C polymorphisms and T1D. This family-based study reports a strong association between possible genotypes of CTLA-4 gene polymorphism and T1D in South Indian population, particularly in younger individuals.     

Investigation of CTLA-4 and CD28 gene polymorphisms in a group of Turkish patients with colorectal cancer

Colorectal cancer (CRC), also called colon cancer or bowel cancer, includes cancerous growths in the colon, rectum and appendix. The immune system is an important defence mechanism against cancer and is often dysfunctional in patients with malignancies. Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) and CD28 genes encode receptors that provide negative and positive signals, respectively. Polymorphisms in these genes can affect their functions. In this study, we aimed to investigate the association of cancer with the frequencies and roles of CTLA-4/+49A > G (exon 1) and -318C > T (promoter), and CD28/IVS3 + 17T > C (intron 3 position + 17). These polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 218 Turkish subjects (56 patients with CRC and 162 healthy controls). No statistically significant differences in the genotype distributions of CTLA-4/+49GG (1.8% vs. 6.8%, odds ratio (OR) = 0.250, P = 0.305) and CTLA-4/-318TT (0% vs. 0.6%, OR = 1.006, P = 1.000), and CD28/IVS3 + 17CC (8.9% vs. 3.7%, OR = 0.2411, P = 0.155) between patients with CRC and healthy controls, were observed. We also found that there were no significant differences in the frequencies of CTLA-4/+49G (18.8% vs. 20.1%, OR = 0.920, P = 0.891) and CTLA-4/-318T (7.1% vs. 4.3%, OR = 1.653, P = 0.314), and CD28/IVS3 + 17C alleles (25.9% vs. 19.1%, OR = 1.353, P = 0.139) between two study groups. Present results suggested that CTLA-4 and CD28 gene polymorphisms did not play an important role in Turkish patients with CRC.     

Promoter region -318 C/ T and -1661 A/G CTLA-4 single nucleotide polymorphisms and type 1 diabetes in North Indians

Single nucleotide polymorphisms (SNPs) of the CTLA-4 gene have been associated with manifestation of type 1 diabetes in several populations. We assessed the association of five SNPs present in the CTLA-4 gene [-318C/T, -1661A/G and -1722C/T in the promoter region, +49A/G in exon 1 and CT60 in the 3' untranslated region (UTR) region] with type 1 diabetes in North Indian subjects. Genotyping was performed in the patients (n = 130) and the healthy control (n = 180) subjects by polymerase chain reaction-fragment length polymorphism analysis using MseI, BbvI, BstEII and NcoI restriction endonucleases for the -318, -1661, -1722, +49 and CT60 SNPs, respectively. The frequency of G alleles at -1661 locus was significantly higher in the patient group compared with the control subjects. Although the frequency of T alleles at -318 SNP was significantly higher in patients with type 1 diabetes compared with the controls, it did not remain significant after Bonferroni correction for the number of alleles tested. The frequencies of C/T alleles and genotypes at -1722C/T and G allele at +49A/G and CT60 SNPs were not significantly different between the patient and the control groups. Of the various possible haplotypes constructed using the five genetic loci tested (-318, -1661, -1722, +49, CT60), the frequency of 'TGTAG' haplotype was significantly higher in the patients when compared with the controls. The results of the present study indicate that the presence of G allele at -1661 locus at the CTLA-4 gene (IDDM12 locus) is associated with increased susceptibility to type 1 diabetes in North Indians, whereas A allele is protective.     

Polymorphisms in Cytotoxic T-lymphocyte Associated Antigen 4 Gene Does Not Affect sCytotoxic T-lymphocyte Associated Antigen 4 Levels in Human Papillomavirus-Infected Women with or without Cervical Cancer

Background: Cervical cancer (CaCx) is the second most common cancer in Indian women. Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) + 49 AA polymorphism is known to be associated with CaCx. Current attempt is to use immunotherapy for the treatment of metastatic melanoma and metastatic castration-resistant prostate cancer, i.e., blocking of CTLA-4 using a fully human monoclonal CTLA-4 antibody to disrupt its inhibitory signal. This allows the CTLs to destroy the cancer cells. There is no information available on the soluble level of CTLA-4 on which the immunotherapy is targeted. This is specifically in Indian population including cases with CaCx. Objective: The aim of this study is to evaluate the levels of soluble CTLA-4 (sCTLA-4) in human papillomavirus (HPV)-infected women with or without CaCx and their association with the polymorphism at CTLA-4 + 49 A/G and CTLA-4 −318 C/T genotypes. Materials and Methods: This is an exploratory case–control study involving two groups of HPV-infected women, the cases were with invasive CaCx and the control group was women with the healthy cervix. sCTLA-4 levels were measured using ELISA in 92 CaCx cases and 57 HPV-positive women with the healthy cervix. Results: Both cases and controls have similar sCTLA-4 levels. Comparison of CTLA-4 + 49A/G and −318 C/T genotypes with sCTLA-4 levels among cases and control also did not show any statistically significant difference. Conclusion: The present study suggests sCTLA-4 levels are not affected by a polymorphism at + 49 A>G CTLA-4. Hence, levels of CTLA-4 are similar in both CaCx cases and control group.     

自身免疫性甲状腺病CTLA—4基因外显子1A／G^49多态性研究

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多态性与自身免疫性甲状腺病（AITDs）的相关性。方法　采用多聚酶链反应限制性片段长度多态性（PCR-RFLP）技术分析122例自身免疫甲状腺病患者,其中Graves’病（GD）87例,桥本甲状腺炎（HT）35例,84例健康对照的CTLA-4基因外显子1的49位点基因型。采用ELISA技术检测AITDs患者甲状腺功能,间接免疫荧光法检测甲状腺球蛋白抗体（TGAb）和甲状腺抗过氧化物酶抗体（TPOAb）。结果　AITDs患者CTLA-4／G