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.     

PTPN22 G788A和A10281188G与广东地区人群RA易感性的关系研究

目的探讨蛋白酪氨酸磷酸酶非受体型22（PTPN22）基因多态性（rs33996649/G788A/R263Q和rs1310182/A10281188G）与广东地区汉族人群类风湿性关节炎（RA）易感性间的关系。方法选取广东地区人群中218例RA患者以及229例健康对照者进行病例对照研究,采用PCR-RFLP技术检测PTPN22G788A和A10281188G两个多态性位点的基因型,计算比较两组基因型和等位基因频率。结果 RA患者和健康对照者PTPN22在788位点均为G等位基因,未检测到A等位基因,没有发现单核苷酸多态性的存在;10281188位点G等位基因在病例组和对照组中的频率分别为12.4%和13.3%（P〉0.05）。结论广东地区人群PTPN22788位点不存在多态性,G788A和A10281188G基因位点与广东汉族人群RA的发病无相关性。     

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单核苷酸多态性在自身免疫性疾病中的研究进展

单核苷酸多态性(single nucleotide polymorphism,SNP)是基因组中一种最常见的遗传变异,可作为新一代遗传标记,成为定位疾病相关基因的有力工具。近年研究发现,蛋白酪氨酸磷酸酶非受体型22(the protein tyrosine phosphatase nonreceptor22,PTPN22)单核苷酸多态性作为自身免疫病的易感基因,在自身免疫性疾病中发挥着重要的作用。     

类风湿性关节炎患者血清IL-6水平及其基因多态性研究

目的: 探讨血清IL-6水平及其基因多态性与类风湿性关节炎(RA)的相关性.方法: 采用酶联免疫吸附法(ELSIA)检测148例RA患者血清IL-6水平,并用序列特异性引物-聚合酶链反应(PCR-SSP)技术检测患者IL-6基因启动子两个位点的等位基因和基因型(IL-6-572C/G、 IL-6-174G/C).与健康对照组(120例)相比较.结果: RA患者血清IL-6水平明显高于对照组(P<0.01),IL-6-174G/C位点CC、 GC与GG基因型分布频率与健康对照组有明显差异(P<0.01),其C等位基因频率高于对照组(P<0.01),IL-6-572C/G位点GG、 GC与CC基因型两组之间比较有统计学意义(P<0.01),其G等位基因频率明显低于健康对照组(P<0.01).结论: RA与患者血清IL-6有关;IL-6-174G/C位点的C等位基因可能是RA发病的独立危险因素,IL-6-572C/G位点的G等位基因-可能有一定保护作用.     

类风湿性关节炎患者Eotaxin-3 +2497基因多态性研究

目的:研究类风湿性关节炎(RA)患者Eotaxin-3 +2497T/G单核苷酸多态性(SNP)。方法:用聚合酶链反应方法对目的基因进行扩增,用单链构象多态性方法进行SNP分析,最后用测序及四引物聚合酶链反应方法对结果进行验证。结果:RA组与对照组Eotaxin-3 +2497位存在TT和TG两种基因型,且基因型分布符合Hardy-Weinberg平衡定律;RA组与对照组Eotaxin-3 +2497位基因型频率及等位基因频率间差异有显著性意义(P<0.05)。结论:RA患者Eotaxin-3 +2497位G等位基因频率明显高于对照组。     

云南汉族人群HLA-B基因多态性与类风湿性关节炎的相关性研究

目的 探讨HLA-B基因多态性与类风湿性关节炎(rheumatoid arthritis,RA)的关联性.方法 采用DNA测序和序列特异性引物聚合酶链式反应(polymerase chain reaction-sequencespecific primer,PCR-SSP)方法检测云南汉族中271例类风湿性关节炎患者和264例正常人群的HLA-B基因多态性并进行关联性分析.结果 女性类风湿性关节炎患者的HLA-B*40基因频率(8.84％)明显低于女性对照组(18.33％)(P=0.000),HLA-B*51基因频率(9.53％)明显高于对照组(2.83％)(P=0.000),HLA-B*48基因频率(0.23％)明显低于对照组(2.33％)(P=0.007),差异均有统计学意义.HLA-B*40、HLA-B*51、HLA-B* 48的基因频率在男性类风湿性关节炎患者和男性对照中的分布无统计学差异(P值分别为0.535、0.691、0.289).结论 云南汉族人群中HLA-B基因分布存在多态性.HLA-B基因多态性与云南汉族人群女性类风湿性关节炎的发病相关,HLA-B*51可能是易感基因,HLA-B*40、HLA-B* 48可能是保护性等位基因.     

海南汉族人群MICB等位基因多态性与类风湿性关节炎相关性研究

目的 研究海南汉族人群MHC I类链相关基因B(MHC class I chain-related gene B,MICB)等位基因多态性与类风湿性关节炎(rheumatoid arthritis,RA)的相关性.方法 用世界卫生组织推荐的标准盐析法提取外周静脉血DNA,采用PCR-序列特异性引物(PCR sequence specific primer,PCR-SSP)和PCR产物直接测序分型(PCR-sequence based genotyping,PCR-SBT)方法对样本MICB基因的多态性进行检测分析.结果 RA患者及对照组中共有10种MICB等位基因被检测出,两组中MICB*005:02等位基因频率分布最高,其频率为52.6％比42.0％,但MICB* 002等位基因频率在RA组明显低于对照组(13.1％比25.5％),差异具有统计学意义(Pc＜0.05),MICB* 014等位基因频率在RA组亦明显低于对照组(8.1％比15.3％),差异具有统计学意义(Pc＜0.05).结论 MICB* 002和MICB*014等位基因与RA的易感性之间存在负相关,可能是RA的保护性基因.     

IL-27 p28基因多态性与中国汉族人群类风湿性关节炎的相关性研究

目的:探讨中国汉族人群IL-27p28基因多态性与类风湿性关节炎易感性的关系。方法:采用聚合酶链式反应PCR技术检测103例类风湿性关节炎患者和104例健康对照者IL-27p28启动子区-964A/G,外显子区2905T/G、g.4730T/C的基因型。计算并对比分析出两组人群的基因型频率和等位基因频率及其分布情况。结果:病例组和对照组的基因型分布均符合Hardy-weinberg平衡定律(P>0.05)。所检测三个位点的基因型频率及等位基因频率在病例组和对照组间的差异均无统计学意义(P>0.05)。结论:IL-27p28基因启动子区和外显子区单核苷酸多态-964A/G和2905T/G、g.4730T/C均未发现与中国汉族人群类风湿性关节炎的易感性有显著关联。     

PTPN22基因多态性与Graves病

弥漫性甲状腺亢进Graves病1是一种多因素引起的疾病,遗传易感性在其发病中起到重要的作用。蛋白酪氨酸磷酸酶非受体型122（protein tyrosine phosphatase non—receptortype22,PTPN22）基因作为其多种自身免疫性疾病的易感基因,被认为通过编码淋巴酪氨酸磷酸酶,在T细胞信号转导中起负性调节作用,可维持免疫系统平衡。而PTPN22的C1858T基因多态性,会使T细胞表面受体的信号减弱和调节性T细胞出现功能缺陷,从而引起Graves病的发生。     

ORIGINAL ARTICLE: PTPN22 C1858T Polymorphism in Women with Endometriosis

Citation Gomes FMCS, Bianco B, Teles JS, Christofolini DM, de Souza AMB, Guedes AD, Barbosa CP. PTPN22 C1858T polymorphismin women with endometriosis. Am J Reprod Immunol 2010; 63: 227–232 Problem Endometriosis has been suggested to be an autoimmune disease and recently, an allelic variation of the PTPN22 (C1858T) gene was revealed to be associated with the development of autoimmunity. The aim of the study was to determine the frequency of the PTPN22 (C1858T) polymorphism in Brazilian women with endometriosis as compared with controls. Method of study Case–control study included 140 women with endometriosis and a control group consisting of 180 healthy fertile women without a history of endometriosis and/or autoimmune diseases from the ABC School of Medicine. The PTPN22 (C1858T) polymorphism was studied by restriction fragment length polymorphism polymerase chain reaction (RFLP‐PCR). Results Genotypes CC, CT and TT of PTPN22 polymorphism presented frequencies of 67.9, 30.0 and 2.1% in the women with endometriosis (P = 0.008); 76.2, 19.0 and 4.8% in women with minimal/mild endometriosis (P = 0.173); 61.0, 39.0 and 0.0% in women with moderate/severe endometriosis (P ≤ 0.001) and 82.8, 16.1 and 1.1% in control group. Allele C and T were present in 82.9 and 17.1%; 85.7 and 14.3%; 80.5 and 19.5%; and 90.8 and 9.2% respectively, in women with endometriosis (P = 0.004), women with minimal/mild endometriosis (P = 0.148), women with moderate/severe endometriosis (P = 0.002) and control group. Conclusion The data suggest that in Brazilian women polymorphism PTPN22 (C1858T) may be an important genetic predisposing factor for endometriosis, especially, in advanced disease.     

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.     

Association between PTPN22 C1858T and type 1 diabetes: a replication in continental Italy

The missense PTPN22 C1858T polymorphism recently emerged as an important population-independent risk factor for type 1 diabetes (T1D) and other autoimmune diseases. The PTPN22 gene encodes the lymphoid tyrosine phosphatase (LYP), a negative regulator of signal transduction through the T-cell receptor. Although the frequency of the polymorphism is variable among different ethnic groups, the association between PTPN22 *T1858 and T1D has been replicated in several populations. Here, we contribute the first replication of the association between PTPN22 and T1D in populations from continental Italy, carried out in two independent samples of T1D patients ( N  = 216 and 82) and controls ( N  = 271 and 89). Our data also suggest that T1D carriers of the *T1858 allele could be at increased risk for other comorbid autoimmune disorders.     

The PTPN22 promoter polymorphism -1123G>C association cannot be distinguished from the 1858C>T association in a Norwegian rheumatoid arthritis material

The protein tyrosine phosphatase nonreceptor 22 (PTPN22) gene has, during the last 2 years, been recognized as a susceptibility gene for numerous autoimmune diseases, including rheumatoid arthritis (RA) and type 1 diabetes. An association between the exonic 1858C>T single nucleotide polymorphism (SNP) and RA has repeatedly been replicated in several Caucasian populations. The SNP is not associated with autoimmune diseases in Asian populations, as the 1858T allele is almost absent. Recently, a promoter polymorphism -1123G>C was proposed to be associated with acute-onset type 1 diabetes in Japanese and Korean populations. Furthermore, in Caucasian populations, the presence of additional PTPN22 risk variants has been suggested, indicating that the 1858C>T risk variant cannot explain the entire disease association observed in the region. In this study, we wanted to jointly address and integrate these separate findings to further elucidate the association between the PTPN22 gene and RA in a Norwegian material of 861 RA patients and 559 healthy controls. Our results revealed that the strength of the association with the PTPN22 promoter polymorphism, -1123G>C, is analogous to that observed for 1858C>T. As the -1123G>C variant is also polymorphic in Asian populations, our data underpin the need to further explore the association between this variant and autoimmune diseases in different populations.     

The 1858T PTPN22 gene variant contributes to a genetic risk of type 1 diabetes in a Ukrainian population

The 1858T variant of the protein tyrosine phosphatase gene, PTPN22, is associated with an increased risk of several autoimmune diseases. The aim of this study has been to investigate the possible association of 1858C-->T PTPN22 polymorphism and type 1 diabetes (T1D) in Caucasians from Ukraine. Overall, the distribution of 1858 PTPN22 genotypes differed significantly between the T1D patient group (n = 296) and the control group (n = 242) (P = 0.0036). When both groups were classified according to sex, the TT genotype and T allele showed a statistically significant higher frequency in T1D female patients (5.9 and 22.8%, respectively) in comparison with the female controls (0 and 11.9%) (P = 0.008 for both analyses). The patients with the TT genotype were significantly younger at the onset of T1D compared with those with genotypes TC and CC (P = 0.035 and 0.019, respectively). In our Ukrainian Caucasian cohort, we confirmed the association between T1D and the PTPN22,1858T allele.     

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.     

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.     

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.     

Identification of susceptibility SNPs in CTLA-4 and PTPN22 for scleritis in Han Chinese

The aim of this study was to determine the association between 13 single nucleotide polymorphisms (SNPs) in the cytotoxic T lymphocyte-associated antigen-4 (CTLA4) and protein tyrosine phosphatase non-receptor type 22 (PTPN22) genes with scleritis in a Chinese Han population. We recruited 432 scleritis patients and 710 healthy controls. Four tag SNPs of CTLA4 and nine tag SNPs of PTPN22 were selected using Haploview. Genotyping was performed with the Sequenom MassArray® iPLEX GOLD Assay. Genotype and allele frequency differences were analyzed by χ² test and Bonferroni correction. Haplotype analysis was performed to further evaluate the association of these two genes with scleritis. In this study, CTLA4/rs3087243 G allele frequency and GG genotype frequency were significantly increased in scleritis patients compared to healthy controls [corrected P-value (Pc) = 0·02, odds ratio (OR) = 1·475, 95% confidence interval (CI) = 1·175–1·851; Pc = 0·04, OR = 1·546, 95% CI = 1·190–2·008, respectively]. None of the tested SNPs in the PTPN22 gene showed an association with scleritis. Haplotype analysis revealed a lower frequency of a CTLA4 TCAA haplotype (order of SNPs: rs733618, rs5742909, rs231775, rs3087243) (Pc = 4·26 × 10^–3, OR = 0·618, 95% CI = 0·540–0·858) and a higher frequency of a PTPN22 TTATACGCG haplotype (order of SNPs: rs3789604, rs150426536, rs1746853, rs1217403, rs1217406, rs3789609, rs1217414, rs3789612, rs2488457) (Pc = 2·83 × 10^–4, OR = 1·457, 95% CI = 1·210-1·754) in scleritis patients when compared to healthy controls. In conclusion, our findings indicate that CTLA4 and PTPN22 might confer genetic susceptibility to scleritis in a Chinese Han population.