PTPN22基因多态性与中国广东汉族人群RA发病的相关性研究

目的检测中国广东地区汉族人群中类风湿关节炎（RA）发病与蛋白酪氨酸磷酸酶非受体型22（PTPN22）基因Arg620Trp／1858C〉T多态性的关系。方法采用PER—RFLP技术分析了广东汉族人群中148例散发RA患者和150例健康对照者PTPN221858位点基因型。结果在中国广东地区汉族人群中PTPN221858位点仅存在等位基因C,与RA的发病无关。结论中国广东地区汉族人群中,PTPN22Arg620Trp多态性与RA的发病无关：PTPN22基因可能存在其他多态性位点,需作进一步探讨。     

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.     

PTPN22 1858C/T基因多态性与肺结核易感性关系的Meta分析

目的 探讨蛋白酪氨酸磷酸酶非受体型22(protein tyrosine phos-phatase nonreceptor 22,PTPN22)1858C/T基因多态性与肺结核(TB)易感性的关联。方法 计算机检索Pubmed、EMABSE、CJFD、CBM、CNKI、VIP及万方数据库,检索时间截至2023年3月1日,收集关于PTPN22 1858C/T基因多态性与肺结核易感性的病例-对照研究,初步筛查出10篇文献。按照纳入和排除标准,由两名评价者分别对相关文献进行选择,以及资料进行提取和进行质量评价,采用RevMan 5.1和Statal 2.0软件进行Meta分析。结果 5个病例-对照研究最终被纳入,其中病例组851例,对照组976例。在本研究的3种遗传模型中,纳入的结果同质性均较好。Meta分析结果在各遗传模型中显示,PTPN22 1858C/T基因多态性与肺结核易感性的关联有统计学意义(显性遗传模型：CT+TT vs CC:OR=0.39,95%CI 0.23～0.67;共显性遗传模型：CT vs CC:OR=0.39,95%CI 0.23～0.67;T vs C:OR=0....     

PTPN11第3内含子基因多态性及H.pylori感染与广西柳州地区胃癌易感性研究

目的探讨蛋白酪氨酸磷酸酶非受体型11（PTPN11）基因多态性及幽门螺杆菌（H.pylori）感染与广西柳州地区胃癌易感性的相关性。方法通过PCR检测H.pylori的尿素酶B亚单位（UreB）基因和两步法聚合酶链反应（PCR-CTPP）对广西柳州地区238例胃癌患者及112例健康对照者的PTPN11基因第3内含子2460位点进行单链构象多态性分析（SNP）。结果胃癌组和对照组H.pylori（＋）者分别为142例（59.7%）和54例（48.2%）,H.pylori（-）者分别为96例（40.3%）和58例（51.8%）,H.pylori感染率在两组间差异有统计学意义（P〈0.05）。胃癌组和对照组PTPN11基因在该位点的基因型频率分布符合遗传平衡状态且差异无统计学意义（P〉0.05）,但两组间的等位基因分布差异有统计学意义（P〈0.05）。与G/G型相比,G/A型和A/A型不能减低胃癌的发病风险（G/A型：OR=0.642,95%CI：0.397～1.039;A/A型：OR=0.399,95%CI：0.097～1.641）;但将G/A型和A/A型合并后与G/G型相比,带有A基因的个体患胃癌的风险显著降低（OR=0.620,95%CI：0.388～0.992）。根据发病年龄、性别、吸烟史、饮酒史和H.pylori感染对胃癌的易感性进行的分层分析发现,PTPN11基因该位点SNP与胃癌的年龄、性别、吸烟史以及饮酒史无关,H.pylori阳性的A基因携带者相对于G/G型个体患胃癌的风险减少到0.52倍（OR=0.521,95%CI：0.274～0.990）。结论广西柳州地区PTPN11基因第3内含子2460位点A基因携带者能明显降低胃癌的发病风险,H.pylori感染与该位点G/G基因型之间存在交互作用。     

CTLA-4基因多态性与Graves病

细胞毒性T淋巴细胞相关抗原4（cytotoxie Tlymphocyte associated antigen4，CTLA-4）是激活的T细胞表达的一种膜蛋白，属免疫球蛋白超家族成员，对T细胞增生起负性调节作用。与抗原呈递细胞（APC）表面的B7分子结合，作为协同刺激信号抑制T细胞增生、活化，诱导T细胞耐受。CTLA-4功能和（或）表达缺陷参与了T细胞介导的自身免疫性疾病的发生发展。Graves病（GD）是一种由于抑制性T淋巴细胞（TS）功能缺陷所导致的器官特异性自身免疫病。近年来研究结果认为，CTLA4基因的多态性与GD有关，CTLA4基因作为GD的易感候选基因已成为研究的热点。     

PTPN2基因单核苷酸多态性与中国东北地区人群溃疡性结肠炎的关系

目的探讨我国东北地区人群PTPN2 rs2542151基因多态性与溃疡性结肠炎(ulcerative colitis,UC)遗传易感性、疾病活动性和严重性的关系。方法收集115例UC患者和99例健康对照者全血,应用TAQMAN探针,Realtime-PCR检测PTPN2 rs2542151位点等位基因多态性。结果 UC组PTPN2 rs2542151 T等位基因频率,G等位基因频率分别为79.13%,20.87%;对照组分别为85.35%,14.65%,差异无统计学意义(0.05)。GG纯合子相对于TT纯合子和TG杂合子UC易感性较健康对照组有显著差异(=0.042)。基因型是TG的患者病情为重度的可能性是GG的11.553倍(0.05)。PTPN2 rs2542151位点基因多态性与UC患者的发病年龄、性别、血红蛋白、血沉、C反应蛋白、血小板、临床分型及发病部位无关(0.05)。结论 PTPN2 rs2542151单核苷酸多态性与中国东北地区人群UC易感性相关,PTPN2 rs2542151基因突变可影响UC的病情严重程度。     

云南人群中PTPN22和PADI4基因多态性与类风湿关节炎的关联研究

目的 探讨云南人群PTPN22和PADI4基因的7个SNP多态与类风湿关节炎易感性的相关性.方法 选取192例类风湿关节炎患者和288名正常人进行病例对照研究.分别用PCR-RFLP法检测PTPN22基因的rs33996649和1858位点、PADI4基因的rs11203366和rs874881位点,用焦磷酸测序法检测PADI4基因的rs1635579、rs2428736和rs2240340共7个SNP位点的基因型.结果 在7个SNP位点中,PADI4基因的rs2240340位点的等位基因频率和基因型频率在病例组和对照组间差异有统计学意义(P＜0.05).结论 在云南人群中PADI4基因的rs2240340多态性与类风湿关节炎的易感性存在相关性.     

类风湿性关节炎相关基因PTPN22 C1858T在中国6个民族中的遗传多态性研究

目的 研究与类风湿性关节炎相关的PTPN22 C1858T在中国蒙古族、满族、达斡尔族、哈萨克族、回族和四川汉族6 个人群中的遗传多态性。方法 应用PCR-RFLP方法检测6 个人群共539个个体中PTPN22 1858T等位基因频率。结果 6个人群中PTPN22 1858T等位基因频率是0.0195（n=539）分布符合Hardy-Weinberg平衡;在蒙古族、满族、达斡尔族、哈萨克族、回族和四川汉族人群中PTPN22 1858T等位基因频率分别是0.0114、0.0143、0、0.0698、0.0216和0且6个人群间差异有统计学意义（P<0.05）。结论 获得了中国6 个人群PTPN22 1858T等位基因频率数据,为评估中国不同人群对类风湿性关节炎的遗传易感性及流行病学研究提供了基本的数据。     

广东人汉族群CTLA-4基因外显子1多态性与Graves病的相关性

目的探讨CTLA-4基因外显子1多态性与广东地区汉族人群Graves病的关系。方法以PCR-RFLP技术观察100名健康人与100例Graves病(GD)患者细胞毒性T淋巴细胞相关抗原4(CTLA-4)基因外显子1的多态性。结果提示GD患者的CTLA-4外显子1的G49等位基因频率较正常对照组显著增高(P<0.01)。结论CTLA-4基因可能是广东地区汉族人群中GD的易感候选基因。     

Graves病候选基因多态性研究进展

Graves病是一种器官特异性自身免疫性疾病，它的病因学十分复杂，是遗传和环境因素相互作用的结果。近几年，人类基因组序列和SNP的研究使这类多基因疾病易感基因的鉴定取得很大进展。目前，Graves病候选基因研究多选择与该病病理过程有关的基因以及甲状腺固有基因，如：HLA系统基因、CTLA-4基因、TSH-R基因、TG基因等，并取得一定进展。本文就这些基因多态性与Graves病关系研究现状进行综述。     

Association study of PTPN22 C1858T polymorphism in Trypanosoma cruzi infection

In this study we investigated a possible role for the single nucleotide polymorphism C1858T of the PTPN22 (protein tyrosine phosphatase nonreceptor 22) gene in determining the susceptibility to Trypanosoma cruzi infection, as well as in development of chagasic heart disease. This study included 316 patients with Chagas' disease and 520 healthy individuals from Colombia and Peru. Genotyping of PTPN22 was performed by the real-time polymerase chain reaction technology, using the TaqMan 5' allelic discrimination assay. No statistically significant differences in the frequency of PTPN22 C1858T gene polymorphism between chagasic patients and controls or between asymptomatic and cardiomyopathic individuals were observed. Our findings suggest that the PTPN22 polymorphism analyzed does not play a major role in the development of Chagas' disease in the Colombian and Peruvian populations.     

Meta-analysis reveals PTPN22 1858C/T polymorphism confers susceptibility to rheumatoid arthritis in Caucasian but not in Asian population

The PTPN22 1858C/T polymorphism is associated with rheumatoid arthritis (RA). However, reports from the Asian populations are conflicting in nature and lacks consensus. The aim of our study was to evaluate the association between the PTPN22 1858C/T polymorphism and RA in Asian and Caucasian subjects by carrying out a meta-analysis of Asian and Caucasian data. A total of 27?205 RA cases and 27?677 controls were considered in the present meta-analysis involving eight Asian and 35 Caucasian studies. The pooled odds ratios (ORs) were performed for the allele, dominant, and recessive genetic model. No statistically significant association was found between the PTPN22 1858C/T polymorphism and risk of RA in Asian population (allele genetic model: OR?=?1.217, 95% confidence interval (CI)?=?0.99–1.496, p value 0.061; dominant genetic model: OR?=?1.238, 95% CI?=?0.982–1.562, p value 0.071; recessive genetic model: OR?=?1.964, 95% CI?=?0.678–5.693, p value 0.213). A significant association with risk of RA in Caucasian population suggesting that T–– allele does confer susceptibility to RA in this subgroup was observed (allele genetic model: OR?=?1.638, 95% CI?=?1.574–1.705, p value p value p value PTPN22 1858C/T polymorphism is not associated with RA risk in Asian populations. However, our meta-analysis confirms that the PTPN22 1858C/T polymorphism is associated with RA susceptibility in Caucasians.     

Association of PTPN22 C1858T Polymorphism and Type 1 Diabetes: A Meta-analysis

Recently, protein tyrosine phosphatase nonreceptor 22 (PTPN22) C1858T polymorphism has been identi?ed as a susceptibile gene for type 1 diabetes (T1D), but studies are inconsistence, In order to assess the association between PTPN22C1858T polymorphism and T1D based on different ethnicities, a meta-analysis was performed, including 26 studies, total of 16,240 patients and 17,997 controls. Meta-analysis was performed on T versus C, T/T+T/C versus C/C (dominant model) and T/T versus T/C+C/C (recessive model) in a ?xed/random effects model. The results indicated an association between the PTPN22 C1858T polymorphism and T1D in all subjects. The overall odds ratio (OR) of T versus C using the fixed effects model was 1.948 (95% CI = 1.859～2.041, P < 0.001). After strati?cation by ethnicity, analysis revealed that the PTPN22 C1858T polymorphism T allele was signi?cantly associated with T1D in Europeans, Americans (OR = 1.946, 95% CI = 1.852～2.045, P < 0.001; OR = 1.946, 95% CI = 1.690～2.242, P < 0.001, respectively). Meta-analysis of the T/T+T/C genotype and the T/T genotypes showed the same results as that shown by the PTPN22 C1858T polymorphism T allele. This meta-analysis suggests a possible association between the PTPN22 C1858T polymorphism and T1D, especially in European and American populations.     

PTPN22 Gene Polymorphism (C1858T) Is Associated with Susceptibility to Type 1 Diabetes: A Meta‐Analysis of 19,495 Cases and 25,341 Controls

The protein tyrosine phosphatase N22 (PTPN22) gene C1858T polymorphism has been reported to be associated with susceptibility to type 1 diabetes (T1D) in relatively small sample sizes. This study aimed at investigating the pooled association by carrying out a meta‐analysis on the published studies. The Medline, EBSCO, and BIOSIS databases were searched to identify eligible studies published in English before June 2012. The association was assessed by odds ratio (OR) with 95% confidence intervals (CI). The presence of heterogeneity and publication bias was explored by using meta‐regression analysis and Begg's test, respectively. A total of 28 studies were involved in this meta‐analysis. Across all populations, significant associations were found between the PTPN22 C1858T polymorphism and susceptibility to T1D under genotypic (TT vs. CC [OR = 3.656, 95% CI: 3.139–4.257], CT vs. CC [OR = 1.968, 95% CI: 1.683–2.300]), recessive (OR = 3.147, 95% CI: 2.704–3.663), and dominant models (OR = 1.957, 95% CI: 1.817–2.108). In ethnicity‐ and sex‐stratified analyses, similar associations were found among Caucasians and within Caucasian male and female strata. The meta‐analysis results suggest that the PTPN22 C1858T polymorphism was associated with susceptibility to T1D among the Caucasian population, and males who carried the ‐1858T allele were more susceptible to T1D than females.     

Type 1 diabetes linked PTPN22 gene polymorphism is associated with the frequency of circulating regulatory T cells

Dysfunction of FOXP3-positive regulatory T cells (Tregs) likely plays a major role in the pathogenesis of multiple autoimmune diseases including type 1 diabetes (T1D). Whether genetic polymorphisms associated with the risk of autoimmune diseases affect Treg frequency or function is currently unclear. Here, we analysed the effect of T1D-associated major HLA class II haplotypes and seven single nucleotide polymorphisms in six non-HLA genes [INS (rs689), PTPN22 (rs2476601), IL2RA (rs12722495 and rs2104286), PTPN2 (rs45450798), CTLA4 (rs3087243), and ERBB3 (rs2292239)] on peripheral blood Treg frequencies. These were determined by flow cytometry in 65 subjects who had progressed to T1D, 86 islet autoantibody-positive at-risk subjects, and 215 islet autoantibody-negative healthy controls. The PTPN22 rs2476601 risk allele A was associated with an increase in total (p = 6 × 10⁻⁶) and naïve (p = 4 × 10⁻⁵) CD4+CD25+CD127lowFOXP3+ Treg frequencies. These findings were validated in a separate cohort comprising ten trios of healthy islet autoantibody-negative children carrying each of the three PTPN22 rs2476601 genotypes AA, AG, and GG (p = 0.005 for total and p = 0.03 for naïve Tregs, respectively). In conclusion, our analysis implicates the autoimmune PTPN22 rs2476601 risk allele A in controlling the frequency of Tregs in human peripheral blood.     

The PTPN22 1858T variant is not associated with primary biliary cirrhosis

The minor allele of a single nucleotide polymorphism (SNP) in the PTPN22 gene (1858T) encoding the Lyp-tyrosine phosphatase has been recently associated with multiple autoimmune disorders, raising the possibility that this variant may also represent a risk allele for primary biliary cirrhosis (PBC). We therefore investigated the possible association of the PTPN22(1858T) variant with PBC in a Canadian population. We studied 160 Caucasian patients with biopsy and antimitochondrial antibodies (AMA)-proven PBC who were genotyped for the PTPN22(C1858T) SNP using a single-base primer extension assay and mass spectrometry. The frequency of the PTPN22(1858T) allele was then compared between the patients and 290 healthy controls. No association was detected between the PTPN22(1858T) allele and PBC, the frequency of this variant being similar in patients with PBC (7.5%) and controls (8.4%). Restricting the analysis to patients with PBC with any second autoimmune condition or specifically with sicca syndrome or autoimmune thyroid disease also revealed no association with this variant. Thus the PTPN22(1858T) variant is not associated with PBC or with the combination of PBC and a second autoimmune disease. These data suggest that this variant does not confer risk for PBC and does not account for the frequent presence of other autoimmune diseases in patients with PBC.     

HLA-DR,HLA-DQB1 and PTPN22 gene polymorphism: association with age at onset for autoimmune diabetes

Introduction

Autoimmune diabetes has different clinical manifestations related to the age at onset. It is divided into several subtypes, including “classical” type 1 diabetes (T1D) and latent autoimmune diabetes in adults (LADA). The LADA is considered a slowly progressing subtype of autoimmune diabetes, although the clinical picture is more similar to type 2 diabetes.

Material and methods

The aim of this study is to investigate whether genetic predisposition influences age at onset in autoimmune diabetes. We studied rs2476601 PTPN22 gene polymorphism and HLA DR, HLA-DQB1 in 175 patients with classical type 1 diabetes, 80 LADA, and 151 control subjects from north-east Poland.

Results

The frequencies of the PTPN22 TT genotype were higher in the group of patients with classical type 1 diabetes (6.3%) and LADA (11.3%) than in control subjects (0.7%) (p = 0.02 and p = 0007, respectively). In patients with classical type 1 diabetes we observed an increasing trend in frequencies of genotype TT dependent on age at onset (3.9% (0-5 year olds), 6.0% (6-15 year-olds), 8.2% (16-25 year olds), p = 0.048). The incidence of predisposing human leukocyte antigen (HLA) genotypes HLA DR3/DQB1*02 and DR4/DQB1*0302 was found to decrease in the group with type 1 diabetes in relation to age at onset and LADA (HLA DR3/DQB1*02 – 69.2% (0-5 year olds), 57.0% (6-15 year olds), 51.0% (16-25 year olds), 46.3% (LADA), p = 0.032; HLA DR4/DQB1*0302 – 80.8% (0-5 year olds), 63.0% (6-15 year olds), 51.0% (16-25 year olds), 43.8% (LADA), p = 0.0003), and to increase for the protective allele DQB1*0602 (0.0% (0-5 year olds), 1.0% (6-15 year olds), 2.0% (16-25 year olds), 6.3% (LADA), p = 0.029).

Conclusions

Thus, age at onset for autoimmune diabetes appears to be related to a combination of predisposing and protective HLA alleles. Against a background of HLA genetic predisposition, other non-HLA loci may influence age at onset for late autoimmune diabetes.     

The functional genetic variation in the PTPN22 gene has a negligible effect on the susceptibility to develop inflammatory bowel disease

The aim of this study was to assess the possible association between the protein tyrosine phosphatase non-receptor 22 (PTPN22) gene 1858C-->T (rs2476601, encoding R620W) polymorphism and inflammatory bowel disease (IBD). Our study population consisted of 1113 IBD [544 ulcerative colitis (UC) and 569 Crohn's disease (CD)] patients and 812 healthy subjects. All the individuals were of Spanish white origin. Genotyping of the PTPN22 gene 1858C-->T polymorphism was performed by real time polymerase chain reaction technology, using TaqMan 5'-allelic discrimination assay. The frequency of the PTPN22 1858T allele in healthy subjects was 6.2% compared with 6.7% in the UC patients and 5.1% in Crohn's patients. No statistically significant differences were observed when the PTPN22 1858C-->T allele and genotype distribution among CD patients, UC patients and healthy controls were compared. These results indicate that the PTPN22 1858C-->T polymorphism does not appear to play a major role in IBD predisposition in our population.     

Phosphotyrosine-dependent association between CD22 and protein tyrosine phosphatase 1C

CD22 is a B lymphocyte-specific cell surface glycoprotein that becomes tyrosine phosphorylated upon B cell activation. To determine if tyrosine phosphorylated CD22 couples signaling through membrane immunoglobulin (mIg) to downstream elements, we looked for molecules coprecipitating with CD22 after anti-Ig stimulation. We found that a 60-kDa molecule was stably associated with CD22 following cross-linking of mIg and have identified this molecule as protein tyrosine phosphatase 1C (PTP1C). The association between PTP1C and CD22 is dependent upon tyrosine phosphorylation of CD22, but does not appear to require tyrosine phosphorylation of PTP1C.     

The functional R620W variant of the PTPN22 gene is associated with celiac disease

The functional (R620W) variant of human PTPN22 (protein tyrosine phosphatase non-receptor 22) gene has been implicated in the risk to several autoimmune disorders, including type 1 diabetes, Graves' disease, rheumatoid arthritis and systemic lupus erythematosus. In an association study of this single nucleotide polymorphism with celiac disease (CD), comparison of 262 young diagnosis patients and 214 adult controls from Spain showed a higher frequency of the minor allele in the CD group (9.7% vs 5.6% in controls; P =  0.018), suggestive of an increased genetic risk to the disease (odds ratio = 1.82; 95% confidence interval 1.1–3.0). These results support the role of PTPN22 as a general autoimmunity locus involved in tolerance induction in the thymus.