Association of PTPN22 gene polymorphism and systemic lupus erythematosus in a cohort of Egyptian patients: impact on clinical and laboratory results

Moez, Pacint; Soliman, Eiman

doi:10.1007/s00296-011-2063-z

Cited by 18 publications

(13 citation statements)

References 18 publications

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“…A mutation (1858C>T) in the P1 region, which causes an amino acid change from arginine to tryptophan at position 620 (R620W), disrupts this physiological interaction and results in a gain of function that inhibits T cell receptor signaling [44]. Associations between this polymorphism and SLE susceptibility have been reported in different populations from Europe such as Sweden [45], Spain [46], Crete [47] and Poland [48] and also in populations from Egypt [49], North America [50] and Colombia [51]. Furthermore, it was observed the association of the mutation R620W with renal manifestations occurrence in SLE patients from Sweden [45] and Egypt [49].…”

Section: Ptpn22mentioning

confidence: 99%

“…Associations between this polymorphism and SLE susceptibility have been reported in different populations from Europe such as Sweden [45], Spain [46], Crete [47] and Poland [48] and also in populations from Egypt [49], North America [50] and Colombia [51]. Furthermore, it was observed the association of the mutation R620W with renal manifestations occurrence in SLE patients from Sweden [45] and Egypt [49]. Another variant (R263Q), located within the catalytic domain of the tyrosine phosphatase and identified as a loss-of-function mutation, was found to reduce the risk of SLE in a multiethnic cohort from Spain, Italy, Argentina and North America [52].…”

Section: Ptpn22mentioning

confidence: 99%

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Systemic Lupus Erythematosus: Old and New Susceptibility Genes versus Clinical Manifestations

Silva¹,

Addobbati²,

Sandrin-Garcia³

et al. 2014

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Systemic Lupus Erythematosus (SLE) is one of the most relevant world-wide autoimmune disorders. The formation of autoantibodies and the deposition of antibody-containing immune complexes in blood vessels throughout the body is the main pathogenic mechanism of SLE leading to heterogeneous clinical manifestations and target tissue damage. The complexity of etiology and pathogenesis in SLE, enclosing genetic and environmental factors, apparently is one of the greatest challenges for both researchers and clinicians. Strong indications for a genetic background in SLE come from studies in families as well as in monozygotic and dizygotic twins, discovering several SLE-associated loci and genes (e.g. IRF5, PTPN22, CTLA4, STAT4 and BANK1). As SLE has a complex genetic background, none of these genes is likely to be entirely responsible for triggering autoimmune response in SLE even if they disclosure a potentially novel molecular mechanisms in the pathogenesis' disease. The clinical manifestations and disease severity varies greatly among patients, thus several studies try to associate clinical heterogeneity and prognosis with specific genetic polymorphisms in SLE associated genes. The continue effort to describe new predisposing or modulating genes in SLE is justified by the limited knowledge about the pathogenesis, assorted clinical manifestation and the possible prevention strategies. In this review we describe newly discovered, as well as the most studied genes associated to SLE susceptibility, and relate them to clinical manifestations of the disease.

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Section: Ptpn22mentioning

confidence: 99%

Section: Ptpn22mentioning

confidence: 99%

Systemic Lupus Erythematosus: Old and New Susceptibility Genes versus Clinical Manifestations

Silva¹,

Addobbati²,

Sandrin-Garcia³

et al. 2014

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show abstract

“…The single nucleotide polymorphisms (SNPs) of PTPN22 , predominantly p.Arg620Trp (c.1858C>T), are among the major causative agents of human autoimmune disorders. Associations of PTPN22 SNPs with type 1 diabetes (T1DM) [3,4,5], latent autoimmune diabetes in adults (LADA) [6,7], autoimmune thyroid diseases (including Graves' disease and Hashimoto's thyroiditis) [8,9,10], rheumatoid arthritis (including anticitrullinated peptide antibody-negative subjects) [11], juvenile idiopathic arthritis [12], systemic lupus erythematosus [13,14,15], thymoma-associated myasthenia gravis [16], antineutrophil cytoplasmic autoantibodies (ANCA) disease [17,18], vasculitis (including ANCA-associated vasculitis, Wegener's granulomatosis and Behçet's disease) [19], chronic spontaneous autoreactive urticaria [20], and generalized vitiligo [21,22,23] have repeatedly been reported. PTPN22 polymorphisms also affect the responses of chronic-phase chronic myeloid leukemia patients to treatment with the tyrosine kinase inhibitor imatinib [24].…”

Section: Introductionmentioning

confidence: 99%

Low Frequencies of Autoimmunity-Associated <b><i>PTPN22</i></b> Polymorphisms in MODY Patients, Including Those Transiently Expressing Islet Cell Autoantibodies

Heneberg¹,

Malá²,

Yorifuji³

et al. 2015

Int Arch Allergy Immunol

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Background: The protein tyrosine phosphatase nonreceptor type 22 (PTPN22) gene encodes lymphoid tyrosine phosphatase (LYP), which is expressed primarily in lymphoid tissues. The functional but geographically highly variable PTPN22 single-nucleotide polymorphisms (SNPs), particularly c.1858C>T, contribute to the onset and progression of autoimmunity-associated diseases and facilitate the expression of disease-associated autoantibodies. In Central Europe, 17-25% of patients with monogenic diabetes (maturity-onset diabetes of the young, MODY) transiently express islet cell autoantibodies. Methods: We addressed the links between the functional and geographically variable PTPN22 SNPs with MODY manifestation and the expression of islet cell autoantibodies in 276 MODY patients who originated from four regions (the Czech Republic, Israel, Japan and Brazil). Results: The frequency of PTPN22 polymorphisms in the MODY patients was similar to those in geographically matched healthy populations, with the exception of c.788G>A, the minor allele frequency of which was significantly elevated in the Czech hepatocyte nuclear factor 1-α (HNF1A) MODY patients [odds ratio (OR) 4.8, 95% confidence interval (CI) 2.2-10.7] and the Brazilian MODY patients (OR 8.4, 95% CI 1.8-39.1). A barely significant increase in the c.788G>A minor allele was also detected in the islet cell autoantibody-positive Czech MODY patients. However, c.788A behaves as a loss-of-function mutant in T cells, and thus protects against autoimmunity. Conclusions: MODY patients (including islet cell autoantibody-positive cases) do not display any increase in autoimmunity-associated PTPN22 alleles. The absence of autoimmunity-associated PTPN22 alleles was also demonstrated in latent autoimmune diabetes in adults, which suggests that the slow kinetics of the onset of autoantibodies is subject to a regulation that is different from that experienced in type 1 diabetes and other autoimmune disorders.

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“…Several studies have identified an association among PTPN22 ?1858C[T polymorphism and increased risk of RA [27][28][29] T1DM [30][31][32] and SLE [33][34][35]. However, PTPN22 ?1858C[T polymorphism prevalence varies significantly in human populations.…”

Section: Discussionmentioning

confidence: 99%

Distribution of PTPN22 polymorphisms in SLE from western Mexico: correlation with mRNA expression and disease activity

et al. 2015

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Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune inflammatory disease characterized by 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 evaluate the genetic contribution of PTPN22 -1123G>C and +1858C>T polymorphisms and their haplotypes in SLE patients, as well as mRNA expression according to -1123G>C promoter polymorphism and disease activity. One hundred and fifty SLE patients and 150 unrelated healthy controls (HC), both Mexican mestizos, were genotyped by PCR-RFLP technique for the PTPN22 -1123G>C and +1858C>T polymorphisms. PTPN22 mRNA expression levels were determined by real-time PCR from PBMCs of thirty patients with SLE and fifteen HC carrying different genotypes. Distributions of genotype and allelic frequencies were similar between SLE and HC. The most frequent alleles were -1123 G and +1858 C in both groups (69 vs. 66 % and 97 vs. 98 %, in SLE and HC, respectively). However, the recessive model of inheritance analysis showed a lower frequency of -1123 CC genotype in SLE patients (7 vs. 15 %), suggesting a protection effect to develop SLE (OR 0.41, CI 1.10-5.28, p = 0.02). Haplotype analysis showed strong linkage disequilibrium D' = 0.98 for PTPN22 -1123G>C and +1858C>T polymorphisms, but haplotypes were not associated with SLE. The PTPN22 mRNA expression did not show differences among -1123G>C genotypes; nevertheless, a significant negative correlation with disease activity was found (r = -0.64, p < 0.01). SLE inactive patients showed similar PTPN22 mRNA expression levels to healthy controls, whereas in patients with severe flare, the expression was nearly depleted. In conclusion, we found a lack of association of PTPN22 -1123G>C and +1858C>T polymorphisms with the risk of developing SLE in a Mexican population. Moreover, decreased or absent PTPN22 mRNA expression in SLE patients with severe flare suggests that Lyp plays an important regulatory role, and its absence contributes to the inflammatory response and disease activity in SLE. However, further analysis in a prospective study could help us determine its usefulness as a genetic marker of disease activity in SLE.

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Association of PTPN22 gene polymorphism and systemic lupus erythematosus in a cohort of Egyptian patients: impact on clinical and laboratory results

Cited by 18 publications

References 18 publications

Systemic Lupus Erythematosus: Old and New Susceptibility Genes versus Clinical Manifestations

Systemic Lupus Erythematosus: Old and New Susceptibility Genes versus Clinical Manifestations

Low Frequencies of Autoimmunity-Associated <b><i>PTPN22</i></b> Polymorphisms in MODY Patients, Including Those Transiently Expressing Islet Cell Autoantibodies

Distribution of PTPN22 polymorphisms in SLE from western Mexico: correlation with mRNA expression and disease activity

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