Protein Tyrosine Phosphatase Non-receptor Type 22 Gene Research Articles

Relationship Between Protein Tyrosine Phosphatase Non-Receptor Type 22 1858>C Gene Polymorphism with Rheumatoid Arthritis Disease Activity Score-28

Background: Rheumatoid arthritis (RA) is one of the systemic inflammatory autoimmune diseases. A number of previous studies showed the potency of Protein Tyrosine Phosphatase Non-Receptor Type 22 (PTPN22) 1858c>T gene polymorphism with the incidence of rheumatoid arthritis. Objective: To know the relationship of PTPN22 1858C>T gene polymorphism with disease activity score-28 (DAS-28) in rheumatoid arthritis patients at H. Adam Hospital Medan. Method: 69 rheumatoid arthritis patients were conducted in this study by consecutive sampling who were treated at H. Adam Malik General Hospital, Medan from February-August 2022. The PTPN22 gene polymorphism was genotyped using polymerase chain reaction. Results: Majority of the subject in the study was female, around 65 people (94.2%). The mean age of the subjects was 42.35 ± 12.28 years old. The most ethnic group was Batak with 34 people (49.3%). Mean DAS-28 score was 3.45 ± 0.79. All CC genotypes and C alleles were found in 69 (100%) subjects. Statistical analysis found no correlation between PTPN22 1858C>T gene polymorphism and DAS-28 score with p value <1.0 Conclusion: PTPN22 1858C>T gene polymorphism has no significant relationship DAS-28 in rheumatoid arthritis. Keywords: PTPN22 1858C>T gene polymorphism, Disease Activity Index-28, rheumatoid arthritis

TiO2 nanoparticles abrogate the protective effect of the Crohn’s disease-associated variation within the PTPN22 gene locus

ObjectiveInflammatory bowel disease (IBD) is a multifactorial condition driven by genetic and environmental risk factors. A genetic variation in the protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene has been...

Correlation Analysis of Th17/Treg Cells and PTPN22 Gene Polymorphism in HT Patients with Different Iodine Nutritional Status

Background: The incidence of Hashimoto's thyroiditis (HT) may be related to environmental, immune, and genetic factors. Different iodine nutritional status can affect thyroid function. Th17/Treg cell imbalance is involved in the pathogenesis of autoimmune thyroid diseases, and PTPN22 is an important susceptibility gene related to autoimmune diseases. To study the relationship between Th17/Treg cells and cytokines and PTPN22 gene polymorphism in HT patients with different iodine nutritional status is to determine the role of immune and genetic factors in the pathogenesis of HT. Objective: To investigate the correlation between Th17/Treg cells and factors protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene-1123G>C site (rs2488457) polymorphism in peripheral blood mononuclear cells (PBMC) of Hashimoto's thyroiditis (HT) patients with different iodine nutritional status. Methods: 100 HT patients and 60 healthy subjects in Cang Zhou are selected from 2019 to 2020. Flow cytometry and real-time fluorescent quantitative PCR are used to detecting the proportion and ratio of Th17 and Treg cells in PBMC, as well as retinoic acid-related orphan receptor-γt (ROR-γt) and fork head/winged spiral transcription factor 3 (Foxp3) mRNA expression levels. Single allele-specific primer-polymerase chain reaction (SASP-PCR) technology is taken to sequence PTPN gene promoter-1123SNP leading to calculate the gene Type and allele frequency. Results: Th17 and Treg cells and factors in the PBMC of HT patients have a certain correlation with the-1123G>C locus of PTPN22 gene (rs2488457). The distribution frequency of rs2488457 genotype is consistent with Hardy Weinberg's law of genetic equilibrium. The distribution frequencies of various genotypes and alleles are significantly different between HT patients and the control group (P<0.05). PTPN22 gene-1123G>C site C/G, C/C genotype can increase of the risk of HT, while G/G genotype can decrease of the risk of HT. In Conclusion: The polymorphism of rs2488457 is related to susceptibility to HT. Carrying C/G and C/C genotypes may be risk factors for HT, and G/G genotypes may be protective factors for HT, but it has nothing to do with iodine nutrition status.

DNA hypermethylation of PTPN22 gene promoter in children and adolescents with Hashimoto thyroiditis

Protein tyrosine phosphatase non-receptor type 22 (PTPN22) is an inhibitor of T-cell activation, regulating intracellular signal transduction and thereby being implicated in the pathogenesis of autoimmune thyroid disease (AITD). The exact molecular mechanisms have not been fully elucidated. The aim of the present study was to quantitate DNA methylation within the PTPN22 gene promoter in children and adolescents with AITD and healthy controls. 60 Patients with Hashimoto thyroiditis (HT), 25 patients with HT and type 1 diabetes (HT + T1D), 9 patients with Graves' disease (GD) and 55 healthy controls without any individual or family history of autoimmune disease were enrolled. Whole blood DNA extraction, DNA modification using sodium bisulfate and quantification of DNA methylation in the PTPN22 gene promoter, based on melting curve analysis of the selected DNA fragment using a Real-Time PCR assay, were implemented. DNA methylation in the PTPN22 gene promoter was found to be significantly higher in HT patients (39.9 ± 3.1%) in comparison with other study groups (20.3 ± 2.4% for HT + T1D, 32.6 ± 7.8% for GD, 27.1 ± 2.4% for controls, p < 0.001). PTPN22 gene promoter DNA methylation was also associated marginally with thyroid autoimmunity in general (p = 0.059), as well as considerably with thyroid volume (p = 0.004) and the presence of goiter (p = 0.001) but not thyroid function tests. This study demonstrates for the first time that a relationship between autoimmune thyroiditis and PTPN22 gene promoter DNA methylation state is present, thus proposing another possible etiological association between thyroiditis and abnormalities of PTPN22 function. Further expression studies are required to confirm these findings.

Quantitative evaluation of PTPN22 copy number variation by digital droplet PCR and association with type 2 diabetes risk.

Type 2 diabetes (T2D) is a chronic endocrine disorder with rapidly increasing prevalence worldwide. Genetic instability leading to metabolic dysfunction plays an important role in T2D susceptibility and progression. Structural alteration in genome, that is, copy number variation (CNV) is emerging as the inherent marker for disease identification. Previous genomic CNV array revealed that protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene was overlapped with a CNV region, however, whether this CNV affected T2D risk remains to be further elucidated. In this study, we first identified divergent distributions of the PTPN22 copy number (CN) between T2D patients and healthy controls in Chinese population (p < 0.01). Risk assessment analysis revealed that the CN gain (OR = 3.28, p < 0.001) was the promising risk factor for T2D. Also, significantly positive correlations of the PTPN22 CNV with fasting plasma glucose and glycated hemoglobin were demonstrated in T2D patients. Statistical association analysis investigated that the T2D individuals carrying CN gain showed higher plasma glucose and lower insulin levels than those carrying CN normal and loss at 60 min/120 min/180 min during an OGTT test. In addition, the PTPN22 CNV had an effect on total cholesterol, and the CN gain presented higher values than the other two CN types. These results suggested that the CN gain types of the PTPN22 gene accompany with the glycometabolism dysregulation, and finally predispose their carriers to T2D; therefore, the PTPN22 CNV may be a promising biomarker for predicting T2D risk, or a clinical target for T2D diagnosis and therapy.

PTPN22 Gene Polymorphisms Are Associated with Susceptibility to Large Artery Atherosclerotic Stroke and Microembolic Signals

Large artery atherosclerotic stroke (LAAS) is the most common ischemic stroke (IS) subtype, and microemboli may be clinically important for indicating increased risk of IS. The inflammatory process of atherosclerosis is well known, and lymphoid phosphatase (Lyp), which is encoded by the protein tyrosine phosphatase nonreceptor type 22 (PTPN22) gene, plays an important role in the inflammatory response. Our study was intended to evaluate the relationship between PTPN22 gene and LAAS and microembolic signals (MES). Three loci of the PTPN22 gene (rs2476599, rs1217414, and rs2488457) were analyzed in 364 LAAS patients and 369 control subjects. A genotyping determination was performed using the TaqMan assay. The G allele of rs2488457 might be related to a higher risk for developing LAAS and MES (odds ratio (OR) = 1.456, 95% confidence interval (CI) 1.156-1.833, P = 0.001; OR = 1.652, 95% CI 1.177-2.319, P = 0.004, respectively). In the LAAS group, the prevalence of the GTG haplotype was higher (P < 0.001) and the prevalence of the GCC haplotype was lower (P = 0.001). An interaction analysis of rs2488457 with smoking showed that smokers with the CG/GG genotypes had a higher risk of LAAS, compared to nonsmokers with the rs2488457 CC genotype (OR = 2.492, 95% CI 1.510–4.114, P < 0.001). Our research indicated that the PTPN22 rs2488457 might be related to the occurrence of LAAS and MES in the Han Chinese population. In addition, the rs2488457 polymorphism and the environmental factor of smoking jointly influenced the susceptibility of LAAS.

The association between rs2476601 polymorphism in PTPN22 gene and risk of alopecia areata: A meta-analysis of case-control studies.

Background:The single nucleotide polymorphism (SNP) rs2476601 of the protein tyrosine phosphatase, nonreceptor type 22 (PTPN22) gene has been presented to implicate in the pathogenesis of alopecia areata (AA) in a few association investigations with limited sample size and inconsistent conclusions.Methods:The aim of the current meta-analysis was to assess and synthesize the presently available data on the connection between rs2476601 and AA vulnerability. Six electronic databases, including EMBASE, PubMed, Web of Science, the Cochrane Library, Wanfang data, and the China National Knowledge Infrastructure database (CNKI), were systematically retrieved for relevant observational studies published previous to November 2018. Total odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs) were analyzed to evaluate the correlation between PTPN22 polymorphism and AA. Risk of bias was estimated according to the Newcastle–Ottawa Scale (NOS). Sensitivity analyses were carried out using the RevMan 5.3 software.Results:In general, 5 case–control studies including 1129 AA patients and 1702 healthy control individuals were obtained for this meta-analysis. The pooled results suggested that rs2476601 SNP was significantly associated with AA susceptibility under allelic model (C vs T, OR = 0.77, 95% CI, 0.64–0.92, P = .003) and recessive model (CC vs CT + TT, OR = 0.73, 95% CI, 0.60–0.88, P = .001).Conclusion:On the basis of the results of the current research, the rs2476601 polymorphism of PTPN22 gene is significantly correlated with AA susceptibility. The C-allele and CC-genotype carriers at this locus have a lower risk of AA.

Identification and structure–function analyses of an allosteric inhibitor of the tyrosine phosphatase PTPN22

Protein-tyrosine phosphatase nonreceptor type 22 (PTPN22) is a lymphoid-specific tyrosine phosphatase (LYP), and mutations in the PTPN22 gene are highly correlated with a spectrum of autoimmune diseases. However, compounds and mechanisms that specifically inhibit LYP enzymes to address therapeutic needs to manage these diseases remain to be discovered. Here, we conducted a similarity search of a commercial database for PTPN22 inhibitors and identified several LYP inhibitor scaffolds, which helped identify one highly active inhibitor, NC1. Using noncompetitive inhibition curve and phosphatase assays, we determined NC1's inhibition mode toward PTPN22 and its selectivity toward a panel of phosphatases. We found that NC1 is a noncompetitive LYP inhibitor and observed that it exhibits selectivity against other protein phosphatases and effectively inhibits LYP activity in lymphoid T cells and modulates T-cell receptor signaling. Results from site-directed mutagenesis, fragment-centric topographic mapping, and molecular dynamics simulation experiments suggested that NC1, unlike other known LYP inhibitors, concurrently binds to a "WPD" pocket and a second pocket surrounded by an LYP-specific insert, which contributes to its selectivity against other phosphatases. Moreover, using a newly developed method to incorporate the unnatural amino acid 2-fluorine-tyrosine and 19F NMR spectroscopy, we provide direct evidence that NC1 allosterically regulates LYP activity by restricting WPD-loop movement. In conclusion, our approach has identified a new allosteric binding site in LYP useful for selective LYP inhibitor development; we propose that the 19F NMR probe developed here may also be useful for characterizing allosteric inhibitors of other tyrosine phosphatases.

876 The association between rs2476601 polymorphism in PTPN22 gene and risk of alopecia areata: A meta-analysis of case-control studies

The single nucleotide polymorphism (SNP) rs2476601 of the protein tyrosine phosphatase, nonreceptor type 22 (PTPN22) gene has been presented to implicate in the pathogenesis of alopecia areata (AA) in a few association investigations with limited sample size and inconsistent conclusions. The aim of the current meta-analysis was to assess and synthesize the presently available data on the connection between rs2476601 and AA vulnerability. Six electronic databases including EMBASE, PubMed, Web of Science, the Cochrane Library, Wanfang data and the China National Knowledge Infrastructure database (CNKI) were systematically retrieved for relevant observational studies published previous to November 2018. Total odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs) were analysed to evaluate the correlation between PTPN22 polymorphism and AA. Risk of bias was estimated according to the Newcastle-Ottawa Scale (NOS). Sensitivity analyses were carried out using the RevMan 5.3 software. In general, 5 case-control studies including 1129 AA patients and 1702 healthy control individuals were obtained for this meta-analysis. The pooled results suggested that rs2476601 SNP was significantly associated with AA susceptibility under allelic model (C vs. T, OR=0.77, 95%CI 0.64-0.92, P=0.003) and recessive model (CC vs. CT+TT, OR=0.73, 95%CI 0.60-0.88, P=0.001). On the basis of the results of the current research, the rs2476601 polymorphism of PTPN22 gene is significantly correlated with AA susceptibility. The C-allele and CC-genotype carriers at this locus have a lower risk of AA.

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.

Association of protein tyrosine phosphatase non-receptor type 22 gene functional variant C1858T, HLA-DQ/DR genotypes and autoantibodies with susceptibility to type-1 diabetes mellitus in Kuwaiti Arabs.

The incidence of type-1 Diabetes Mellitus (T1DM) has increased steadily in Kuwait during recent years and it is now considered amongst the high-incidence countries. An interaction between susceptibility genes, immune system mediators and environmental factors predispose susceptible individuals to T1DM. We have determined the prevalence of protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene functional variant (C1858T; R620W, rs2476601), HLA-DQ and DR alleles and three autoantibodies in Kuwaiti children with T1DM to evaluate their impact on genetic predisposition of the disease. This study included 253 Kuwaiti children with T1DM and 214 ethnically matched controls. The genotypes of PTPN22 gene functional variant C1858T (R620W; rs2476601) were detected by PCR-RFLP method and confirmed by DNA sequencing. HLA-DQ and DR alleles were determined by sequence-specific PCR. Three autoantibodies were detected in the T1DM patients using radio-immunoassays. A significant association was detected between the variant genotype of the PTPN22 gene (C1858T, rs2476601) and T1DM in Kuwaiti Arabs. HLA-DQ2 and DQ8 alleles showed a strong association with T1DM. In T1DM patients which carried the variant TT-genotype of the PTPN22 gene, 93% had at least one DQ2 allele and 60% carried either a DQ2 or a DQ8 allele. Amongst the DR alleles, the DR3-DRB5, DR3-3, DR3-4 and DR4-4 showed a strong association with T1DM. Majority of T1DM patients who carried homozygous variant (TT) genotype of the PTPN22 gene had either DR3-DRB5 or DRB3-DRB4 genotypes. In T1DM patients who co-inherited the high risk HLA DQ, DR alleles with the variant genotype of PTPN22 gene, the majority were positive for three autoantibodies. Our data demonstrate that the variant T-allele of the PTPN22 gene along with HLA-DQ2 and DQ8 alleles constitute significant determinants of genetic predisposition of T1DM in Kuwaiti children.

High prevalence of protein tyrosine phosphatase non-receptor N22 gene functional variant R620W in systemic lupus erythematosus patients from Kuwait: implications for disease susceptibility

BackgroundSystemic lupus erythematosus (SLE) is an autoimmune inflammatory disease which involves the loss of self-tolerance with hyperactivation of autoreactive T- and B-cells. Protein tyrosine phosphatase non-receptor type 22 (PTPN22) encodes for lymphoid specific phosphatase (LYP) which is a key negative regulator of T lymphocyte activation. The aim of this study was to investigate the association between PTPN22 gene functional variant R620W and systemic lupus erythematosus (SLE) by comparing its prevalence in Kuwaiti SLE patients and controls.MethodsThe study included 134 SLE patients and 214 controls from Kuwait. The genotypes of PTPN22 gene functional variant R620W were determined by PCR-RFLP and confirmed by DNA sequence analysis in both SLE patients and the controls.ResultsA relatively high prevalence of the variant 620 W (T-allele) of the PTPN22 gene was detected in the SLE patients from Kuwait. 35.7% of the SLE patients had at least one variant allele (T-allele) compared to 15.9% in the controls. A statistically significant difference was detected in the frequency of variant genotypes, TT and CT between SLE patients and the controls (p < 0.0001). No association was detected between the PTPN22 gene variant and the Raynaud’s phenomenon, renal involvement and severity of the SLE.ConclusionsThe frequency of PTPN22 gene functional variant R620W reported in this study is amongst the highest compared to other world populations. A high prevalence of this variant in SLE patients in comparison to the healthy controls suggests its significant contribution in conferring susceptibility to SLE together with other factors.

Protein tyrosine phosphatase nonreceptor type 22 (PTPN22) gene single nucleotide polymorphisms and its interaction with T2DM on pulmonary tuberculosis in Chinese Uygur population.

AimsTo investigate the association of several single nucleotide polymorphisms (SNPs) within Protein tyrosine phosphatase nonreceptor type 22 (PTPN22) gene and additional gene- gene and gene- type 2 diabetes mellitus (T2DM) interaction with pulmonary tuberculosis (PTB) risk in Chinese Uygur population.MethodsA total of 722 participants (186 males, 536 females) were selected, including 360 PTB patients and 362 control participants. Generalized multifactor dimensionality reduction (GMDR) was used to screen the best interaction combination among SNPs and T2DM. Logistic regression was performed to investigate association between 3 SNPs within PTPN22 gene, additional gene- gene and gene- T2DM interaction on PTB risk.ResultsLogistic regression analysis showed that PTB risk was significantly lower in carriers with rs2476601- CT genotype than those with CC genotype (CT versus CC), adjusted OR (95%CI) =0.42 (0.17-0.83), and higher in carriers with the rs33996649- GA genotype than those with GG genotype (GA versus GG), adjusted OR (95%CI) = 5.66 (2.24-9.47). We found a significant two-locus model (p=0.0010) involving rs33996649 and T2DM. Overall, the cross-validation consistency of this two- locus model was 10/ 10, and the testing accuracy was 60.11%. We also conducted stratified analysis for rs33996649 and T2DM using logistic regression. We found that T2DM patients with rs33996649 - GA genotype have the highest PTB risk, compared to non- T2DM patients with rs33996649- GG genotype, OR (95%CI) = 4.52 (2.71 -6.43), after covariates adjustment.ConclusionsWe found that the T allele of rs2476601 and the A allele of rs33996649within PTPN22 gene, interaction between rs2476601 and T2DM were all associated with increased PTB risk.

Genotype-Phenotype Associations of the CD-Associated Single Nucleotide Polymorphism within the Gene Locus Encoding Protein Tyrosine Phosphatase Non-Receptor Type 22 in Patients of the Swiss IBD Cohort.

BackgroundProtein tyrosine phosphatase non-receptor type 22 (PTPN22) plays an important role in immune cell function and intestinal homeostasis. The single nucleotide polymorphism (SNP) rs2476601 within the PTPN22 gene locus results in aberrant function of PTPN22 protein and protects from Crohn’s disease (CD). Here, we investigated associations of PTPN22 SNP rs2476601 in inflammatory bowel disease (IBD) patients in the Swiss IBD Cohort Study (SIBDCS).Methods2’028 SIBDCS patients (1173 CD and 855 ulcerative colitis (UC) patients) were included. The clinical characteristics were analysed for an association with the presence of the PTPN22 SNP rs2476601 genotypes ‘homozygous variant’ (AA), ‘heterozygous’ (GA) and ‘homozygous wild-type’ (GG).Results13 patients (0.6%) were homozygous variant (AA) for the PTPN22 polymorphism, 269 (13.3%) heterozygous variant (GA) and 1’746 (86.1%) homozygous wild-type (GG). In CD, AA and GA genotypes were associated with less use of steroids and antibiotics, and reduced prevalence of vitamin D and calcium deficiency. In UC the AA and GA genotype was associated with increased use of azathioprine and anti-TNF antibodies, but significantly less patients with the PTPN22 variant featured malabsorption syndrome (p = 0.026).ConclusionOur study for the first time addressed how presence of SNP rs2476601 within the PTPN22 gene affects clinical characteristics in IBD-patients. Several factors that correlate with more severe disease were found to be less common in CD patients carrying the A-allele, pointing towards a protective role for this variant in affected CD patients. In UC patients however, we found the opposite trend, suggesting a disease-promoting effect of the A-allele.

Role of the C1858T polymorphism of protein tyrosine phosphatase non-receptor type 22 (PTPN22) in children and adolescents with type 1 diabetes.

In recent years, increasing interest has been devoted to the susceptibility gene polymorphisms in type 1 diabetes (T1D) as well as in other autoimmune diseases. Among these, a nucleotide polymorphism of the gene encoding for the protein tyrosine phosphatase non-receptor type 22 (PTPN22) has been associated with T1D in several studies. The aim of this study is to define the frequency of the C1858T polymorphism in the PTPN22 gene in a cohort of 113 Caucasian patients (58 males and 55 females) with T1D, and to assess a possible correlation with a group of clinically relevant variables: age at onset, gender, diabetes-related autoantibodies, residual β-cell function and daily insulin requirement (IR) 6 months after diagnosis. Using a PCR-RFLP approach, we evidenced a 17.7% frequency of the PTPN22 C1858T polymorphism in diabetic patients, higher than the frequency showed in the general population. A statistically significant correlation between this polymorphism and higher levels of C-peptide at diagnosis and lower IR at 6 months from diagnosis was observed (P=0.001 and P=0.04). Moreover, 1858T variant carriers were more frequently positive for glutamic acid decarboxylase (GAD) autoantibodies at diagnosis than wild-type subjects (P=0.19). On the other hand, no significant difference regarding age at onset, gender distribution, insulinoma-associated 2 molecule (IA2) and islet cell antibodies (ICA) positivity was found. These findings, if adequately confirmed in the future and extended to larger samples, may characterize a subset of T1D patients with a defined genetic pattern, who may be eligible for trials aimed to preserve residual β-cell function in the coming years.

Genetic Variations of PTPN2 and PTPN22: Role in the Pathogenesis of Type 1 Diabetes and Crohn's Disease.

Genome wide association studies have identified several genes that might be associated with increase susceptibility to Type 1 Diabetes (T1D) and Crohn's disease. Both Crohn's disease and T1D have a profound impact on the lives of patients and it is pivotal to investigate the genetic role in patients acquiring these diseases. Understanding the effect of single nucleotide polymorphisms (SNP's) in key genes in patients suffering from T1D and Crohn's disease is crucial to finding an effective treatment and generating novel therapeutic drugs. This review article is focused on the impact of SNP's in PTPN2 (protein tyrosine phosphatase, non-receptor type 2) and PTPN22 (protein tyrosine phosphatase non-receptor type 22) on the development of Crohn's disease and T1D. The PTPN2 gene mutation in T1D patients play a direct role in the destruction of beta cells while in Crohn's disease patients, it modulates the innate immune responses. The PTPN22 gene mutations also play a role in both diseases by modulating intracellular signaling. Examining the mechanism through which these genes increase the susceptibility to both diseases and gaining a better understanding of their structure and function is of vital importance to understand the etiology and pathogenesis of Type 1 Diabetes and Crohn's disease.

Association of protein tyrosine phosphatase non receptor type 22 (PTPN22) C1858T gene polymorphism with type 1 diabetes mellitus in Egyptian children cohort

BackgroundThe protein tyrosine phosphatase non receptor 22 gene (PTPN22) is an important negative regulator of signal transduction through the T-cell receptors. Recently a single-nucleotide polymorphism (SNP) 1858 C/T within this gene was shown to be a risk factor for several autoimmune diseases. AimTo analyze a possible association between 1858 C/T SNP and T1DM in Egyptian cohort. Patients and methodsPatients with T1DM and healthy controls were genotyped for the 1858 C/T SNP in PTPN22 gene. ResultsA non-significant association between PTPN22 1858 C/T SNP and T1DM was found. 1858T/T genotype was not observed more frequently in T1DM patients compared to control subjects. ConclusionIn concordance with previous data establishing PTPN22 1858 C/T SNP association with several autoimmune diseases, our findings deny further evidence that the PTPN22 gene may play an important role in the susceptibility to T1DM.

The association of polymorphic sites in some genes with type 1 diabetes mellitus in a sample of Egyptian children

BackgroundThe major histocompatibility complex (MHC) genes have been implicated as the major genetic component in the predisposition to type 1 diabetes mellitus (T1DM). Other loci outside the MHC had also been reported to contribute in the susceptibility of T1DM. The aim of this study was to examine the role of some variants of polymorphic sites in some genes associated with T1DM in a sample of Egyptian children. Patients and methods60 patients with T1DM from the diabetes clinic at Alexandria University Children’s Hospital, and 60 healthy individuals were enrolled in this study. Genomic DNA was extracted using isopropanol precipitation method. Interleukin 18 (IL-18), interleukin 10 (IL-10), vitamin D receptor (VDR), protein tyrosine phosphatase non-receptor type 22 (PTPN22) and cytotoxic T-lymphocyte antigen-4 (CTLA-4) were genotyped. ResultsThe findings obtained from logistic regression analysis suggest that the IL-18 single nucleotide polymorphisms SNP-137 G>C (rs#187238), the VDR Fok1 SNP T>A (rs#2228570) and the SNP-1123 C>G (rs#2488457) in PTPN22 gene showed a significant difference between patients and controls (P=0.026, 0.030, and 0.003, respectively). The genotype distributions of PTPN22 SNP-1858, CTLA-4 SNP 49, IL-10 SNP-819, IL-18 SNP-607, and VDR BsmI SNP G>A did not show any significant difference. ConclusionThe IL-18 SNP-137 G>C (rs#187238), VDR SNP-Fok1 T>A (rs#2228570), and the SNP-1123 C>G (rs#2488457) in PTPN22 gene may have an effect on the occurrence of T1DM in Egyptian children. Further large-scale, population-based, case-control studies are needed.

Role of PTPN22 and VDR gene polymorphisms in susceptibility to rheumatoid arthritis: a study from central India

Role of PTPN22 and VDR gene polymorphisms in susceptibility to rheumatoid arthritis: a study from central India Smriti Shukla,1 Arvind Kumar Tripathi,1 Jitendra Kumar Tripathi,1 Manoj Indurkar,2 Ugam Kumari Chauhan1 1Centre for Biotechnology Studies, Awadhesh Pratap Singh University, Rewa, Madhya Pradesh, India; 2Department of Medicine, Shyam Shah Medical College, Rewa, Madhya Pradesh, India Abstract: Rheumatoid arthritis (RA) is an autoimmune disorder which can be characterized by chronic inflammation of the joints. All joints of the body are prime targets for RA. Several genes which are associated with immunomodulatory functions could be associated with RA as well. In the present investigation we selected the genes which are involved in immunoregulation such as PTPN22 (protein tyrosine phosphatase, non-receptor type 22 (lymphoid)), and VDR (vitamin D receptor), and investigated the impacts of their polymorphism in RA susceptibility. One hundred and twelve patients were enrolled and 125 controls from similar ethnicity were selected for the present investigation. Genetic polymorphism was detected through the PCR-RFLP (polymerase chain reaction restriction fragment length polymorphism) method. The pattern of genotype, allele distribution, and carriage rate in the disease and control groups suggested a significant association of PTPN22-1858 T (rs2476601) carriage (carriage of &ldquo;TT&rdquo; and &ldquo;CT&rdquo;) in RA susceptibility. The pattern of genotype and allele distribution in the disease and control groups suggested a lack of association of VDR FokI (rs10735810) in RA susceptibility. Our findings revealed that the PTPN22 polymorphism is associated with RA, while, the VDR polymorphism is not associated with RA susceptibility. Keywords: rheumatoid arthritis, autoimmune disorder, genetic polymorphism, VDR, PTPN22

A variant within intron 1 of the PTPN22 gene decreases the genetic susceptibility of ankylosing spondylitis in a central south Chinese Han population

Objectives: The protein tyrosine phosphatase non-receptor type 22 (PTPN22) is generally accepted as a key factor in maintaining immune cellular homeostasis. So far, no association has been reported between the polymorphisms of PTPN22 and ankylosing spondylitis (AS) in Chinese populations. We attempted to explore the association between the PTPN22 gene and AS in a central south Chinese Han population.Method: Our study involved 180 HLA-B27+ unrelated patients and 360 HLA-B27– healthy individuals. Seven single nucleotide polymorphisms (SNPs: rs2476601, rs1217414, rs1217418, rs1746853, rs1970559, rs3765598, and rs3811021) were detected. Genotyping was conducted using the polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP) method.Results: rs2476601 was not polymorphic enough in both patients and controls. The SNP rs1217414 was found to be associated with AS but the other five of the seven selected SNPs (rs1217418, rs1746853, rs1970559, rs3765598 and rs3811021) were not.Conclusions: The PTPN22 gene might be associated with AS in a central south Chinese Han population.