The PTPN22 C1858T functional polymorphism and autoimmune diseases--a meta-analysis

Lee, Young Ho; Rho, Young Hee; Choi, Sung Jae; Ji, Jong Dae; Song, Gwan Gyu; Nath, Swapan K.; Harley, John B.

doi:10.1093/rheumatology/kel170

Cited by 283 publications

(204 citation statements)

References 53 publications

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“…Their presumed low-expression or low-activity genotypes predispose to multiple autoimmune diseases, including type 1 diabetes, [5][6][7][8][9] Graves' disease, 7,8 hypothyroidism, 6,8 systemic lupus erythematosus, 6,10 rheumatoid arthritis, 6,11 and non-thymoma myasthenia gravis (MG). 12 However, the function of PTPN22 in this tolerance failure 13 has become debatable because of the paradoxically stronger inhibition of T-cell activation 14 by the autoimmunity-prone PTPN22 þ 1858T/T ( 620 W) or C/T genotype rather than the protective þ 1858C/C ( 620 R). A previous study on French subjects showed an association of the PTPN22 þ 1858C/T single nucleotide polymorphism with non-thymoma MG without anti-titin antibodies but not with thymoma-associated MG. 12 It has been found that interleukin-2 (IL-2) is expressed in the thymus during T-cell receptor (TCR)-mediated thymocyte apoptosis, and IL-2/IL-2 receptor (IL-2R) signaling is required for intrathymic negative selection of T cells.…”

Section: Introductionmentioning

confidence: 99%

The PTPN22gain-of-function+1858T(+) genotypes correlate with low IL-2 expression in thymomas and predispose to myasthenia gravis

et al. 2009

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Section: Introductionmentioning

confidence: 99%

The PTPN22gain-of-function+1858T(+) genotypes correlate with low IL-2 expression in thymomas and predispose to myasthenia gravis

et al. 2009

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“…The protein tyrosine kinase non-receptor (PTPN22) gene has been confirmed as a second RA susceptibility gene in white Caucasian populations, increasing the risk of RA by 40-70%. Interestingly, the variant has not been found in Far Eastern populations (8). Both the HLA-DRB1 and PTPN22 genes are important in immune function and both predispose to other autoimmune diseases, such as type 1 diabetes and systemic lupus erythematosus, as well as RA (9).…”

Section: Introductionmentioning

confidence: 99%

Effect of the human leukocyte antigen HLA-DRB1 and anti-cyclic citrullinated peptide on the outcome of rheumatoid arthritis patients

Farouk

Mansour

Rahman

et al. 2009

Braz J Med Biol Res

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Our objective was to determine whether the presence of the human leukocyte antigen HLA-DRB1 locus is associated with production of anti-cyclic citrullinated peptide antibodies (anti-CCP Abs) and to what extent they are associated with increased susceptibility to and severity of rheumatoid arthritis (RA) in Egyptian patients. Twenty-nine RA patients gave informed consent to participate in a case-control study that was approved by the Ain Shams University Medical Ethics Committee. RA disease activity and severity were determined using the simplified disease activity index and Larsen scores, respectively. We used a wide scale national study on the pattern of HLA typing in normal Egyptians as a control study. Anti-CCP Abs and HLA-DRB1 typing were determined for all subjects. The alleles most strongly associated with RA were HLA-DRB1 [*01 , *04 and *06] (41.4%). RA patients with serum anti-CCP Ab titers above 60 U/mL had a significantly higher frequency of HLA-DRB1*01 (58.3%) and HLA-DRB1*04 alleles (83.3%). Significant positive correlations were found between serum and synovial anti-CCP Ab titer, RA disease activity, and severity (r = 0.87, 0.66 and 0.63, respectively; P < 0.05). HLA-DRB1 SE+ alleles [*01 and *04] were highly expressed among Egyptian RA patients. The presence of these alleles was associated with higher anti-CCP Ab titer, active and severe RA disease. Early determination of HLA-DRB1 SE+ alleles and serum anti-CCP Ab could facilitate the prediction of the clinical course and prognosis of RA when first evaluated leading to better disease control.

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“…Numerous studies have been performed since Bottini et al (17) first discovered the influence of the PTPN22 gene on autoimmune diseases (17). PTPN22 is a strong inhibitor of T cell activation and may therefore affect susceptibility to autoimmunity; it has been implicated in a number of autoimmune and inflammatory diseases (17,27,28).…”

Section: Discussionmentioning

confidence: 99%

Protein Tyrosine Phosphatase Non-receptor 22 Gene C1858T Polymorphism in Patients with Coexistent Type 2 Diabetes and Hashimoto’s Thyroiditis

Bulut¹,

Erol²,

Elyas³

et al. 2014

Balkan Med J

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Autoimmune thyroid diseases and diabetes mellitus exist together more often in comparison to other diseases. The existence ratio increases with age and affects autoimmune diabetics and females the most (1), while thyroid disorders are observed in about 10-15% of patients with diabetes mellitus and 6% of non-diabetics (2). Hashimoto's thyroiditis (HT), also known as chronic lymphocytic thyroiditis or chronic autoimmune thyroiditis (3), is the most common autoimmune thyroid disease, affecting up to 10% of the general population. It is more prevalent in females than in males (4, 5). HT is characterized by the development of autoantibodies against thyroid peroxidase (TPO), thyroglobulin, and thyroid stimulating hormone receptor (TSHR) autoantigens. T cells play a vital role in the pathogenesis of the disease by reacting with thyroid antigens and secreting inflammatory cytokines. So, lymphocytic infiltration of the thyroid, gradual loss of thyroid function and goiter are frequently observed (4). Also, a hypoechogenic and inhomogeneous parenchyma can appear in ultrasound observation of the thyroid gland (5).The observation of thyroid dysfunction in patients with type 1 diabetes mellitus (T1DM) is more frequent than those with type 2 diabetes mellitus (T2DM). Moreover, more than Background: A protein tyrosine phosphatase non-receptor type 22 (PTPN22) C1858T gene polymorphism has been reported to be associated with both Type 2 diabetes mellitus (T2DM) and Hashimoto's thyroiditis (HT) separately. However, no study has been conducted to explore the C1858T polymorphism in T2DM and HT coexistent cases up to now. Aims: The study aimed to determine whether a relationship exists or not between the PTPN22 C1858T polymorphism and this coexistent patient group. Study Design: Case-control study. Methods: Peripheral blood samples from 135 T2DM patients, 102 patients with coexistent T2DM+HT, 71 HT patients and 135 healthy controls were collected into ethylenediaminetetraacetic acid (EDTA) anticoagulant tubes and genomic DNA was extracted. The PTPN22 C1858T polymorphism was analyzed using polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP) methods. Results: Statistically significant differences were not observed between the patient and control groups. This study demonstrated a statistically significant association between both the CT genotype and the T allele in the female patient group with coexistent T2DM+HT (CT genotype: p=0.04; T allele: p=0.045) with a statistically significant association between the CT genotype and the mean values of body mass index (BMI) and free T3 levels (FT3) (BMI: p=0.044 and FT3: p=0.021) that was detected in the patient group with coexistent T2DM+HT. The minor genotype TT was observed in none of the groups in this study. The CT genotype frequency was [number (frequency): 5 (3.8%), 7 (6.86%), 5 (7.04%), 3 (2.22%), while the T allele frequency was 5 (1.86%), 7 (3.44%), 5 (3.53%) and 3 (1.12%)] in the T2DM, T2DM+HT, HT and control groups, respectively. Conclusion: Our data sugge...

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The PTPN22 C1858T functional polymorphism and autoimmune diseases--a meta-analysis

Abstract: This meta-analysis demonstrates that the PTPN22 1858T allele confers susceptibility to RA, SLE, GD, T1D and JIA, supporting evidence of association of the PTPN22 gene with subgroup of autoimmune diseases.

Cited by 283 publications

References 53 publications

The PTPN22gain-of-function+1858T(+) genotypes correlate with low IL-2 expression in thymomas and predispose to myasthenia gravis

The PTPN22gain-of-function+1858T(+) genotypes correlate with low IL-2 expression in thymomas and predispose to myasthenia gravis

Effect of the human leukocyte antigen HLA-DRB1 and anti-cyclic citrullinated peptide on the outcome of rheumatoid arthritis patients

Protein Tyrosine Phosphatase Non-receptor 22 Gene C1858T Polymorphism in Patients with Coexistent Type 2 Diabetes and Hashimoto’s Thyroiditis

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