<i>PTPN22</i> and rheumatoid arthritis: Gratifying replication

Gregersen, Peter K.; Batliwalla, Franak

doi:10.1002/art.21125

Cited by 31 publications

(24 citation statements)

References 30 publications

(33 reference statements)

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“…Patients of this third group are also characterized by a constant expression of anti-titin autoantibodies. 9 As seen in Table 2, the group of nonthymoma patients with early onset and lacking anti-titin antibodies displayed an increased frequency of the risk T allele (13.7%) compared with the control population (7 In contrast, the other two groups of patients, those with a thymoma, and the nonthymoma patients with late-onset of disease and with anti-titin antibodies, showed no significant difference of their allele and genotype frequencies when compared with the control group. Although these two groups were of smaller size, they provided us with reasonable power, 72% in nonthymoma patients with anti-titin antibodies and 65% in thymoma patients, to detect an effect of the magnitude observed in the first group of MG patients at the 5% level of significance.…”

Section: Genotyping and Data Analysismentioning

confidence: 96%

“…This polymorphism changes an arginine (R) into a tryptophane (W) at position 620 of the protein and impairs its binding to the protein tyrosine kinase Csk, resulting in increased T-cell activation. 4 The minor T allele has been associated initially with type 1 diabetes, 4 and subsequently with several other autoimmune diseases, including rheumatoid arthritis, juvenile idiopathic arthritis, systemic lupus erythematosus, autoimmune thyroid diseases, vitiligo, and Addison's disease (see reviews [5][6][7] ). However, other diseases, currently including multiple sclerosis, Crohn's disease, psoriasis, and primary Sjögren's syndrome, appear not to be associated with this variant.…”

mentioning

confidence: 99%

“…To explain this pattern of associations, it was proposed that the PTPN22*620W variant might be a risk factor mainly for autoimmune diseases with a humoral component. 6,7 Even though autoantibodies against the AChR complex are the common effector arm in almost all MG patients, 2,3 this disease is markedly heterogeneous with regard to associated anomalies of the thymus, age at onset of the disease, and the antigens targeted by serum autoantibodies. 8 -11 This heterogeneity significantly influences the genetic associations, especially at the HLA complex.…”

mentioning

confidence: 99%

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Association of the PTPN22*R620W polymorphism with autoimmune myasthenia gravis

Vandiedonck

Capdevielle

Giraud

et al. 2006

Annals of Neurology

107

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Section: Genotyping and Data Analysismentioning

confidence: 96%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Association of the PTPN22*R620W polymorphism with autoimmune myasthenia gravis

Vandiedonck

Capdevielle

Giraud

et al. 2006

Annals of Neurology

107

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“…For example, the association of PTPN22-Arg620Trp with rheumatoid arthritis (RA) has now been replicated in multiple Caucasian populations (Gregersen and Batliwalla 2005), but this allele is not found in Japanese (Mori et al 2005).…”

Section: Population Differencementioning

confidence: 99%

Role of B cell inhibitory receptor polymorphisms in systemic lupus erythematosus: a negative times a negative makes a positive

2006

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B lymphocytes play a pivotal role in the pathogenesis of systemic lupus erythematosus (SLE). Here, we will review our studies on the role of polymorphisms of two genes coding for B cell inhibitory receptors, FCGR2B and CD72. In FCGR2B, a single nucleotide polymorphism leading to a nonsynonymous substitution, Ile232Thr, within the transmembrane domain was identified, and a significant association of the 232Thr/Thr genotype with SLE was observed in Japanese, Thai and Chinese populations, while this allele was found to be rare in Caucasians. On the other hand, the association of FCGR2B promoter polymorphism with SLE in Caucasians has been reported by two independent groups, but this allele was not found to be present in Japanese. These observations demonstrate that the association of FCGR2B polymorphisms with SLE is common to multiple populations, but the alleles associated with SLE depend upon the genetic background of each population. Functional analyses using a human B cell line lacking endogenous FccRIIb revealed that SLE-associated 232Thr allele product was partially excluded from membrane lipid rafts under resting conditions and after coligation with B cell receptor, and was significantly less potent at inhibiting B cell activation. Two haplotypes were identified in CD72, one of which was associated with increased production of an alternative splicing isoform that substantially alters the extracellular region of CD72. Interestingly, the presence of the haplotype significantly decreased the risk of SLE conferred by FCGR2B-232Thr in an epistatic manner. These observations emphasize the need to understand human immune system diversity if we are to improve our understanding of the pathogenesis of autoimmune diseases.

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“…Tal es el caso de los estudios de asociación para artritis reumatoide llevados a cabo en población japonesa, los cuales han señalado evidencia significativa para alelos de los genes PADI4 y SLC22A4 (53,75); tales hallazgos no han sido reproducidos en población caucásica (96). La asociación más robusta descrita para un gen no-MHC ha sido la variante 620W del gen PTPN22, replicada en un amplio número de poblaciones de origen caucásico (97). Sin embargo, este gen prácticamente no es polimórfico en población asiática (98).…”

Section: Genes Candidatosunclassified

Epidemiología genética de la artritis reumatoide: ¿qué esperar de América Latina?

et al. 2011

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La artritis reumatoide es una enfermedad sistémica autoinmune, crónica, que afecta principalmente las articulaciones que tienen movimiento. La enfermedad es mucho más frecuente en mujeres y su prevalencia en la población latinoamericana es cercana al 0,5%. La existencia de agregación familiar (λ s = 2-17) indica su carácter hereditario. Sin embargo, la herencia de la artritis reumatoide es poligénica y no sigue un patrón mendeliano. La importancia de encontrar factores genéticos asociados con la artritis reumatoide radica en la contribución a la comprensión de los mecanismos patogénicos de la enfermedad, su posible aplicación clínica como marcadores de riesgo, diagnóstico, pronóstico, e incluso, blanco terapéutico. Mapeos genéticos llevados a cabo en diversas poblaciones en busca de loci y genes candidatos han identificado la región HLA como aquella con mayor evidencia de ligamento. Sin embargo, su fracción etiológica corresponde sólo a un tercio de la susceptibilidad genética de la enfermedad. Esto indica que genes diferentes al HLA también están implicados en la susceptibilidad a desarrollar artritis reumatoide. En Latinoamérica, los alelos HLA-DRB1*0404 y TNF -308A han sido asociados de manera uniforme con la artritis reumatoide. En el presente artículo se revisan los factores genéticos de la artritis reumatoide en el marco de una aproximación lógica y ordenada establecida por la epidemiología genética, y se ofrecen algunas recomendaciones para futuros estudios en poblaciones latinoamericanas.Palabras clave: artritis reumatoide, epidemiología, enfermedades autoinmunes, complejo mayor de histocompatibilidad, antígenos HLA, América Latina. Genetic epidemiology of rheumatoid arthritis: What to expect from Latin America?Rheumatoid arthritis is a chronic and systemic autoimmune disease characterized by inflammation and destruction of the synovial joints. It affects approximately 0.5% of the LatinAmerican population and is three times more common in women than in men. Evidence of familial aggregation (λ s =2-17) was the first indication of a genetic susceptibility to disease. As in other autoimmune diseases, it has a complex genetic basis. Results from whole-genome scans indicate that the HLA region contains a significant and consistent set of linked loci. However, HLA accounts for only one-third of the genetic susceptibility of disease, indicating that non-HLA genes are also involved in the disease susceptibility. In Latin-America, association with HLA-DRB1*0404 and TNF -308A alleles has been uniformly established; however, many other candidate genes remain to be studied. The identification of genetic factors conferring susceptibility to rheumatoid arthritis will contribute to the knowledge of the pathogenic mechanisms, ability to predict its occurrence, the development of diagnostic tools, prognosis, and treatment. The genetic epidemiology of rheumatoid arthritis is herein reviewed; a set of recommendations is provided for the design, analysis and interpretation of genetic association studies in the context of La...

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PTPN22 and rheumatoid arthritis: Gratifying replication

Cited by 31 publications

References 30 publications

Association of the PTPN22*R620W polymorphism with autoimmune myasthenia gravis

Association of the PTPN22*R620W polymorphism with autoimmune myasthenia gravis

Role of B cell inhibitory receptor polymorphisms in systemic lupus erythematosus: a negative times a negative makes a positive

Epidemiología genética de la artritis reumatoide: ¿qué esperar de América Latina?

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