Protein Tyrosine Phosphatase Nonreceptor 22 C1858T Research Articles

The Association Between the PTPN22 C1858T Variant and Vasculitis: A Meta-analysis Update with Trial Sequential Analysis.

Objective: The present study was designed to determine whether the protein tyrosine phosphatase non-receptor 22 (PTPN22) C1858T variant is associated with susceptibility to vasculitis. Methods: A meta-analysis was conducted to evaluate the association between the PTPN22 C1858T variant and vasculitis. A trial sequential analysis was performed to evaluate the robustness of the meta-analysis. Results: A total of 17 studies were included in this meta-analysis which revealed a highly significant association between the PTPN22 T allele and vasculitis of multiple types (odds ratio [OR] = 4.850, 95% confidence interval [CI] = 3.043-7.729, p < 0.001). Meta-analysis by vasculitis type showed an association between the T allele and risk of giant cell arteritis (GCA) and antineutrophil cytoplasmic antibody-associated vasculitis (AAV) (OR = 7.505, 95% CI = 3.605-15.62, p < 0.001; OR = 6.121, 95% CI = 3.216-11.65, p < 0.001). The meta-analysis also indicated an association between the T allele and Takayasu's arteritis, but not between the T allele and Behcet's disease or Henoch-Schönlein purpura. TSA indicated that the observed association is conclusive with the existing evidence. Conclusions: This meta-analysis confirms that the PTPN22 C1858T variant is associated with susceptibility to GCA and AAV.

Association between PTPN22 C1858T polymorphism and juvenile idiopathic arthritis: A meta-analysis update with trial sequential analysis.

Our aim was to determine whether protein tyrosine phosphatase nonreceptor 22 (PTPN22) C1858T polymorphism (rs2476601) is associated with susceptibility to juvenile idiopathic arthritis (JIA). MEDLINE and EMBASE databases were searched to identify articles in which PTPN22 C1858T polymorphism was reported to be identified in JIA patients and controls. A meta-analysis was conducted to evaluate the association between PTPN22 C1858T polymorphism and RA using allelic contrast. Trial sequential analysis (TSA) was performed. Sixteen separate comparisons involving 5696 JIA patients and 9483 controls (a total of 15,179 subjects) were considered in this meta-analysis. A meta-analysis was performed with all JIA patients as well as JIA patients in each ethnic group. Meta-analysis revealed an association between the T allele of PTPN22 C1858T polymorphism and JIA in all subjects (OR, 1.322; 95% CI, 1.233-1.418; p<.001). Analysis after stratification by ethnicity indicated that the T allele was significantly associated with JIA in the European population (OR, 1.312; 95% CI, 1.2211-1.410; p<.001). However, analysis performed in the non-European population showed no significant association between the T allele and JIA. TSA indicated that the observed association between the PTPN22 polymorphism and JIA in all subjects and the European population is consistent with the existing evidence. This meta-analysis confirms that PTPN22 C1858T polymorphism is associated with susceptibility to JIA in Europeans, and that no additional studies are needed to verify these results. However, current evidence in the non-European population is insufficient, and further studies are warranted.

Association of the single nucleotide polymorphism C1858T of the PTPN22 gene with unexplained recurrent pregnancy loss: A case-control study

Background Lymphoid-tyrosine-phosphatase which is encoded by the protein tyrosine phosphatase non-receptor 22 (PTPN22) gene plays a pivotal role in the regulation of immune responses by dephosphorylating several signaling intermediates of immune cells.ObjectiveSince a balanced immune response has been shown to be important during pregnancy, the purpose of this research was to compare the frequency of the PTPN22 C1858T polymorphism in women with unexplained recurrent pregnancy loss (URPL) vs. in a control group for the first time.Materials and MethodsGenomic DNA from 200 individuals with URPL and 200 individuals without URPL (the control group) at the infertility center in Yazd, Iran was isolated using the salting-out method. The PTPN22 C1858T polymorphism of the two groups was analyzed using polymerase chain reaction-restriction fragment length polymorphism. Genotype frequencies in the women with URPL and the fertile control group were compared using the Chi-square test.ResultsThere were significant differences in the frequency of the PTPN22 1858T polymorphism in the URPL individuals vs. the healthy controls, i.e. 32.0% and 21.5%, respectively (p = 0.01).ConclusionOur findings suggest that the PTPN22 1858T polymorphism could play a role in recurrent pregnancy loss. Therefore, genotyping of the mentioned polymorphism can help clinicians to predict the probable risk of URPL.

Association of Functional Polymorphism in Protein Tyrosine Phosphatase Nonreceptor 22 (PTPN22) Gene with Vitiligo.

The protein tyrosine phosphatase nonreceptor 22 (PTPN22) is associated with susceptibility to autoimmune diseases. The functional polymorphism in PTPN22 at 1857 is a strong risk factor for vitiligo susceptibility in Europeans; however, controversy exits in other populations. Present study was aimed to determine whether the PTPN22 C1857T polymorphism confers susceptibility to vitiligo in Saudi Arabians. Genomic DNA was extracted and amplified using tetra primer amplification-refractory mutation system polymerase chain reaction (ARMS-PCR) method. The frequencies of allele T and genotype CT of PTPN22 C1858T polymorphism were significantly higher, whereas those of allele C and genotype CC were lower in patients as compared with controls (P < 0.0001). The genotype TT was absent in both the patients and controls. It is concluded that PTPN22 C1858T polymorphism is strongly associated with vitiligo susceptibility. However, additional studies are warranted using large number of samples from different ethnicities and geographical areas.

Role of C1858T Polymorphism of Lymphoid Tyrosine Phosphatase in Egyptian Children and Adolescents with Type 1 Diabetes.

Type 1 Diabetes Mellitus (T1DM) is a multifactorial autoimmune disease. The Protein Tyrosine Phosphatase Non-receptor 22 (PTPN22) gene is an important negative regulator of signal transduction through the T-cell Receptors (TCR). A PTPN22 polymorphism, C1858T, has been found to be a risk determinant for several autoimmune diseases, including T1DM, in different populations. The present study was aimed to analyze a possible association between the C1858T polymorphism in Egyptian children with T1DM. This case-control study included 240 children divided evenly between T1DM patients and controls. The PTPN22 C1858T polymorphism was genotyped using polymerase chain reaction with Restriction Fragment Length Polymorphism (RFLP). Both the 1858CΤ and 1858ΤΤ genotypes and the 1858T allele were found more frequently in patients (32.5% and 18.7%, respectively) than in controls (10% and 5.0%, respectively), P=0.013 and P=0.007, respectively. Among females, the 1858T allele was more common in patients (18%) than in controls (2.6%), P=0.014. These findings suggest that the PTPN22 1858T allele could be a T1DM susceptibility factor in the Egyptian population and that it might play a different role in susceptibility to T1DM according to gender in T1DM patients.

AB0250 IL-6, IL-10 and PTPN22 gene polymorphism in children with juvenile idiopathic arthritis

BackgroundJuvenile idiopathic arthritis (JIA) is heterogenous group of diseases and it is most common rheumatic disease in children. Inflammatory cytokines and their regulatory gene polymorphisms are important in the pathogenesis...

THU0109 The PTPN22 C1858T Polymorphism and Rheumatoid Arthritis: A Meta-Analysis

BackgroundThe protein tyrosine phosphatase nonreceptor 22 (PTPN22) gene encodes a lymphoid-specific phosphatase (Lyp). Lyp is an intracellular PTP, and physically binds through its proline-rich motif to the SH3 domain of...

The PTPN22 1858T allele but not variants in the proximal promoter region ofIL-21gene is associated with the susceptibility to type 1 diabetes and the presence of autoantibodies in a Brazilian cohort

Interleukin (IL)-21 and protein tyrosine phosphatase non-receptor 22 (PTPN22) regulate lymphocyte function and have been implicated in the pathogenesis of autoimmune diabetes. We sequenced the proximal promoter of the IL-21 gene for the first time and analysed the PTPN22 1858T polymorphism in type 1A diabetes (T1AD) patients and healthy controls (HC). We correlated the frequencies of islet and extra-pancreatic autoantibodies with genotypes from both loci. The case series comprised 612 T1AD patients and 792 HC. Genotyping of PTPN22 C1858T was performed on 434 T1AD patients and 689 HC. The -448 to +83 base pairs (bp) region of the IL-21 gene was sequenced in 309 Brazilian T1AD and 189 HC subjects. We also evaluated human leucocyte antigen (HLA) DR3/DR4 alleles. The frequencies of glutamic acid decarboxylase (GAD65), tyrosine phosphatase-like protein (IA)-2, anti-nuclear antibody (ANA), thyroid peroxidase (TPO), thyroglobulin (TG), thyrotrophin receptor autoantibody (TRAb), anti-smooth muscle (ASM) and 21-hydroxylase (21-OH) autoantibodies were higher in T1AD patients than in HC. The PTPN22 1858T allele was associated with an increased risk for developing T1AD [odds ratio (OR) = 1·94; P < 0·001], particularly in patients of European ancestry, and with a higher frequency of GAD65 and TG autoantibodies. HLA-DR3/DR4 alleles predominated in T1AD patients. A heterozygous allelic IL-21 gene variant (g.-241 T > A) was found in only one patient. In conclusion, only PTPN22 C1858T polymorphism and HLA-DR3 and/or DR4 alleles, but not allelic variants in the 5'-proximal region of the IL-21 gene were associated with T1AD risk. Patients with T1AD had increased frequencies of anti-islet-cell, anti-thyroid, anti-nuclear, anti-smooth muscle and anti-21-OH autoantibodies. The C1858T PTPN22 polymorphism was also associated with a higher frequency of GAD65 and TG autoantibodies.

The PTPN22 C1858T polymorphism and rheumatoid arthritis: a meta-analysis

The aim of this study was to determine whether the protein tyrosine phosphatase nonreceptor 22 (PTPN22) C1858T polymorphism confers susceptibility to rheumatoid arthritis (RA) in populations with different ethnicities. MEDLINE database and manual search were utilized to identify articles in which the PTPN22 polymorphism was determined in RA patients and controls. A meta-analysis was conducted on the associations between the PTPN22 C1858T polymorphism and RA using (1) allelic contrast and (2) dominant model. A total of 30 separate comparisons involving 17,961 RA patients and 18,611 controls were considered in this meta-analysis. Meta-analysis showed an association between the T allele and RA in all subjects (OR = 1.490, 95% CI = 1.332-1.668, P < 1.0 × 10(-9)). After stratification by ethnicity, analysis indicated that the T allele was significantly associated with RA in Europeans and in Non-Europeans (OR = 1.423, 95% CI = 1.260-1.605, P = 1.0 × 10(-8); OR = 1.902, 95% CI = 1.488-2.430, P = 2.8 × 10(-8)). Meta-analysis of the CT + TT genotype showed the same result patterns as that shown by the PTPN22 C1858T polymorphism T allele. Furthermore, a direct comparison between rheumatoid factor (RF)-positive and RF-negative subjects revealed a significant association with the T allele in RA patients with RF, but not in subjects without RF (OR = 1.561, 95% CI = 1.373-1.775, P < 1.0 × 10(-9)). This meta-analysis confirms that the PTPN22 C1858T polymorphism is associated with RA susceptibility in different ethnic groups, especially in Europeans, and the PTPN22 C1858T polymorphism T allele is significantly more prevalent in RF-positive patents than in RF-negative patients.

The CTLA-4 +49 A/G, CT60 A/G and PTPN22 1858 C/T polymorphisms and susceptibility to vitiligo: a meta-analysis

The aim of this study was to explore whether cytotoxic T lymphocyte antigen-4 (CTLA-4) +49 A/G, CT60 A/G, and protein tyrosine phosphatase nonreceptor 22 (PTPN22) 1858 C/T polymorphisms confer susceptibility to vitiligo. A meta-analysis was conducted of the associations between the CTLA-4 +49 A/G, CT60 and PTPN22 1858 C/T polymorphisms and vitiligo using; (1) allele contrast, (2) the recessive model, (3) the dominant model, and (4) the additive model. A total of 14 separate comparisons were considered in our meta-analysis consisting of 3,404 patients with vitiligo and 5,069 controls (nine studies with 1,252 cases and 2,152 controls for the CTLA-4 polymorphisms and five studies with 1,800 cases and 3,269 controls for the PTPN22 polymorphism). Meta-analysis showed no association between vitiligo and the CTLA-4 +49 A/G polymorphism in all study subjects (OR of the G allele = 1.186, 95 % CI = 0.893-1.575, p = 0.240) and in European (OR = 1.016, 95 % CI = 0.873-1.182, p = 0.838). However, meta-analysis of the CTLA-4 CT60 A/G polymorphism showed an association between vitiligo and the CTLA-4 CT60 G allele in all study subjects (OR = 1.267, 95 % CI = 1.110-1.447, p = 4.5 × 10(-5)) and in the European group (OR = 1.345, 95 % CI = 1.163-1.556, p = 6.3 × 10(-6)). Analysis using the recessive model and homozygote contrast showed the same pattern for the CTLA-4 CT60 G allele. Meta-analysis of the PTPN22 1858 C/T polymorphism showed an association between the PTPN22 T allele and vitiligo in all subjects (OR = 1.507, 95 % CI = 1.320-1.720, p < 1.0 × 10(-8)) and in European group (OR = 1.530, 95 % CI = 1.339-1.748, p < 1.0 × 10(-8)), but not in Asians (OR = 0.482, 95 % CI = 0.152-1.530, p = 0.216). Analysis using the recessive, dominant model, and homozygote contrast showed the same pattern for the PTPN22 T allele. This meta-analysis demonstrates that the CTLA-4 CT60 A/G polymorphism confers susceptibility to vitiligo in Europeans, but no association was found between the CTLA-4 +49 A/G polymorphism and vitiligo susceptibility. The PTPN22 C1858T polymorphism is associated with vitiligo susceptibility in European population.

Meta-analysis of the family-based association between the PTPN22 C1858T polymorphism and Type 1 diabetes

The aim of this study was to determine whether the functional protein tyrosine phosphatase nonreceptor 22 (PTPN22) C1858T polymorphism (rs2476601) confers susceptibility to type 1 diabetes (T1D). We conducted a meta-analysis of the transmission disequilibrium test (TDT) examining preferential transmission of the T allele of the PTPN22 C1858T polymorphism to children with T1D. A total of 11 studies were included in this meta-analysis, which contained 3,946 families and 2,024 transmissions of the PTPN22 T allele in 11 European populations. The frequencies of the transmitted and non-transmitted T allele were 1,250 (61.8 %) and 774 (38.2 %), respectively. The T allele was transmitted to T1D offspring more often than expected. Meta-analysis showed a significant association between the PTPN22 T allele and T1D (OR 1.611, 95 % CI 1.421, 1.827, p < 1 × 10(-8)) without between-study heterogeneity (I(2) = 32.5, p = 0.138). Publication bias was observed in this meta-analysis (Egger's regression test, p-values = 0.061), but the adjusted OR calculated using the trim and fill technique remained significant (OR 1.577, 95 % CI 1.392, 1.785). This meta-analysis of TDT confirms that the PTPN22 C1858T polymorphism is associated with T1D susceptibility in Europeans.

The protein tyrosine phosphatase nonreceptor 22 C1858T polymorphism and vasculitis: a meta-analysis

The aim of this study was to determine whether the functional protein tyrosine phosphatase nonreceptor 22 (PTPN22) C1858T polymorphism (rs2476601) confers susceptibility to vasculitis. A meta-analysis was conducted on the PTPN22 C1858T polymorphism across nine comparative studies containing 1,922 vasculitis patients and 11,505 normal control subjects. Meta-analysis showed no association between the T allele and vasculitis in all subjects [odds ratio (OR) 1.046, 95 % confidence interval (CI) 0.755-1.1.451, p = 0.786], and analysis after stratification by ethnicity indicated that the T allele was not associated with vasculitis in Europeans (OR 1.104, 95 % CI 0.798-1.528, p = 0.551). However, meta-analysis showed a significant association between the T allele and anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) (OR 1.415, 95 % CI 1.228-1.630, p = 1.59 × 10(-6)) and Wegener's granulomatosis (WG) (OR 1.829, 95 % CI 1.377-2.431, p = 3.09 × 10(-5)). In addition, meta-analysis showed an association between the T allele and WG in ANCA-positive subjects (OR 2.042, 95 % CI 1.534-2.719, p = 1.02 × 10(-6)), but not in ANCA-negative WG patients (OR 0.595, 95 % CI 0.199-1.781, p = 0.353). This meta-analysis does not show that the PTPN22 C1858T polymorphism is associated with vasculitis susceptibility, but does show that this polymorphism is associated with susceptibility to AAV, WG, and ANCA status in WG.

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

Recently, protein tyrosine phosphatase nonreceptor 22 (PTPN22) C1858T polymorphism has been identified 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 fixed/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 stratification by ethnicity, analysis revealed that the PTPN22 C1858T polymorphism T allele was significantly 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.

Association of Protein Tyrosine Phosphatase Nonreceptor 22 (PTPN22) C1858T gene polymorphism with susceptibility to autoimmune thyroid diseases: a meta-analysis

Results from studies on the association of PTPN22 C1858T polymorphism with AITD risk are conflicting, we thereby perform this meta-analysis to derive a more precise effect on this possible association. Two investigators independently searched the PubMed, Embase, Wanfang and CNKI (China National Knowledge Infrastructure) databases. A total of 11 studies with 3764 AITDs cases and 3328 controls were finally identified. Statistically significant association was observed between PTPN22 C1858T polymorphism and AITD risk based on all studies (TT vs. CC, OR=2.18, 95%CI=1.31˜3.62; TC vs. CC, OR=1.50, 95%CI=1.29˜1.73; TT/TC vs. CC, OR=1.41, 95%CI=1.12˜1.78; TT vs. TC/CC, OR=2.00, 95%CI=1.21˜3.33). The results of subgroup analysis showed that: (1) regarding ethnic diversity, the variant genotypes TT/TC of C1858T were associated with a significantly increased AITD risk in Caucasians (TT/TC vs. CC, OR=1.41, 95%CI=1.09˜1.83) (2) regarding different countries, the statistically significantly association was observed in UK (TC vs. CC, OR=1.64, 95%CI=1.36˜1.98; TT/TC vs. CC, OR=1.65, 95%CI=1.37˜1.98) and other countries (including South Tunisia, Russia, Polish, Japanese) (TT vs. CC, OR=3.65, 95%CI=1.43˜9.33; TT vs. TC/CC, OR=3.41, 95%CI=1.34˜8.65). (3) regarding the subtypes of AITDs, patients with Graves' disease (GD) had a significant higher degree of C1858T polymorphism (TT vs. CC, OR=2.35, 95%CI=1.36˜4.05; TC vs. CC, OR=1.46, 95%CI=1.12˜1.89; TT/TC vs. CC, OR=1.54, 95%CI=1.33˜1.80; TT vs. TC/CC, OR=2.16, 95%CI=1.25˜3.72), while no association was observed in patients with Hashimoto's thyroiditis (HT). No publication bias was observed. Our results demonstrated that PTPN22 C1858T polymorphism was associated with AITD risk, especially in Caucasians.

The association between the PTPN22 C1858T polymorphism and rheumatoid arthritis: a meta-analysis update

The aim of this study was to determine whether the protein tyrosine phosphatase nonreceptor 22 (PTPN22) C1858T polymorphism confers susceptibility to rheumatoid arthritis (RA) in populations with different ethnicities. A meta-analysis was conducted on the PTPN22 C1858T polymorphism involving eighteen studies, which in total contained 20344 RA patients and 21828 controls. Meta-analysis revealed an association between the PTPN22 C1858T polymorphism T allele and RA in all subjects (odds ratio [OR]=1.637, 95% confidence interval [CI]=1.514-1.770, P<0.001). After stratification by ethnicity, analysis indicated that the PTPN22 C1858T polymorphism T allele was significantly associated with RA in Europeans and Non-Europeans (OR=1.587, 95% CI=1.486-1.696, P<0.001; OR=1.748, 95% CI=1.274-2.398, P<0.001). Meta-analysis of the CT+TT genotype showed the same result patterns as that shown by the PTPN22 C1858T polymorphism T allele. Furthermore, a direct comparison between rheumatoid factor (RF)-positive and -negative subjects revealed a significant association with the T allele in RA patients with RF, but not in subjects without RF. In conclusion, this meta-analysis confirms that the PTPN22 C1858T polymorphism is associated with RA susceptibility in different ethnic groups, especially in Europeans, and the PTPN22 C1858T polymorphism T allele is significantly more prevalent in RF-positive patents than in RF-negative patients.

The association between the PTPN22 C1858T polymorphism and systemic sclerosis: a meta-analysis

The aim of this study was to determine whether the functional protein tyrosine phosphatase nonreceptor 22 (PTPN22) C1858T polymorphism (rs2476601) confers susceptibility to systemic sclerosis (SSc) in different ethnic populations. A meta-analysis was conducted on the PTPN22 C1858T polymorphism across twelve comparative studies containing 4,367 SSc patients and 4,771 normal control subjects. The analysis showed an association between the PTPN22 1858T allele and SSc in all study subjects (OR [odds ratio] 1.169, 95% confidence interval [CI] 1.051, 1.300, P = 0.004). Analysis after stratification by ethnicity indicated that the PTPN22 1858T allele was significantly associated with SSc in Europeans (OR 1.147, 95% CI 1.029, 1.278, P = 0.013), and analysis showed an association between the T allele and SSc in anti-centromere antibody (ACA)-positive European subjects (OR 1.220, 95% CI 1.051, 1.417, P = 0.009). However, no association was found between the allele and anti-topoisomerase antibody (ATA)-positive SSc European patients (OR 1.1786, 95% CI 0.979, 1.417, P = 0.083). In addition, African Americans were found to have a much lower prevalence of the T allele (1.5%) than any other population studied, and Europeans had the highest prevalence (8.2%). This meta-analysis confirms that the PTPN22 C1858T polymorphism is associated with SSc susceptibility and ACA status in Europeans, and that its prevalence is dependent on ethnicity.

The association between the PTPN22 C1858T polymorphism and systemic lupus erythematosus: a meta-analysis update

The aim of this study was to determine whether the functional protein tyrosine phosphatase nonreceptor 22 (PTPN22) C1858T polymorphism (rs2476601) confers susceptibility to systemic lupus erythematosus (SLE) in ethnically different populations. A meta-analysis was conducted on the PTPN22 C1858T polymorphism across 11 comparative studies. Meta-analysis showed an association between the PTPN22 1858T allele and SLE in all study subjects (odds ratio (OR) 1.560, 95% confidence interval (CI) 1.336, 1.822, p = 2.0 × 10(-8)). Analysis after stratification by ethnicity indicated that the PTPN22 1858T allele was significantly associated with SLE in Europeans and Hispanics (OR 1.490, 95% CI 1.280, 1.735, p = 2.0 ×10(-8); OR 2.355, 95% CI 1.644, 3.373, p = 2.9 × 10(-6)). The meta-analysis showed that the C/T + T/T genotype was associated with susceptibility to SLE in all study subjects, Europeans, and Hispanics populations, and an association between the T/T genotype with SLE in Europeans. African Americans had a much lower prevalence of the T allele (2.2%) than any other population studied, and Europeans had the highest frequency (9.5%). In conclusion, this meta-analysis confirms that the PTPN22 C1858T polymorphism is associated with SLE susceptibility in different ethnic groups, and that its prevalence is ethnicity dependent.

The PTPN22 C1858T (R620W) Functional Polymorphism in Kidney Transplantation

To investigate the association between kidney transplant rejection and PTPN22 (protein tyrosine phosphatase non-receptor 22) polymorphism, genomic DNA of 175 renal transplant recipients and 100 healthy blood donors were genotyped by restriction fragment length polymorphism-polymerase chain reaction. The patients were classified in two groups: G1 included 33 HLA-identical recipients and G2 included 142 with one or more HLA mismatches. Forty-nine patients developed an acute rejection episode (ARE): 8 in G1 and 41 in G2. The allelic frequencies of PTPN22 R620W revealed a significant difference between patients and controls. In fact, the W-allele was significantly more frequent in graft recipients than in blood donors (0.05 vs 0.01, P < .05). Furthermore, the frequency of this allele was increased in G1 patients with an ARE (0.188) compared with those without an ARE (0.040), but the difference was not statistically significant. Thus, we concluded that the PTPN22 W-variant allele could be involved in the susceptibility to acute allograft rejection in Tunisian kidney transplant patients.

Association between PTPN22 and endometriosis

PTPN22 is currently one of the few known shared-autoimmunity genes and is therefore a candidate marker for endometriosis. Our data show that female carriers of the PTPN22( *)T variant are significantly more susceptible to endometriosis than controls.

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.