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PDCD1 and CTLA4 polymorphisms affect the susceptibility to, and clinical features of, chronic immune thrombocytopenia.
Br J Haematol ; 180(5): 705-714, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29359792
ABSTRACT
Programmed death-1 (PD-1, PDCD1) and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4, CTLA4) play central roles in immune checkpoint pathways. Single nucleotide polymorphisms (SNPs) of PDCD1 and CTLA4 have been reported to be associated with susceptibility to some autoimmune diseases. However, the potential association between SNPs in these immune checkpoint genes and risk of chronic immune thrombocytopenia (cITP) remain controversial and obscure. The aims of this study were to clarify the influence of PDCD1 and CTLA4 SNPs on the risk of developing cITP and its clinical features. We obtained genomic DNA from 119 patients with cITP and 223 healthy controls; their genotypes were determined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Patients with cITP had a significantly higher frequency of the PDCD1 +7209 TT genotype compared with healthy controls. The CTLA4 -1577 GG genotype and CT60 GG genotype showed higher frequencies of platelet count <5 × 109 /l at diagnosis, minimum platelet count <5 × 109 /l, and bleeding symptoms. Moreover, the PDCD1 -606 AA genotype and +63379 TT genotype were significantly associated with a lower number of patients who achieved a complete response to prednisolone treatment. Our results suggest that the immune checkpoint polymorphisms may affect the susceptibility to the clinical features of cITP, and treatment response of the affected patients.
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Texto completo: Disponible Colección: Bases de datos internacionales Base de datos: MEDLINE Asunto principal: Púrpura Trombocitopénica Idiopática / Polimorfismo de Nucleótido Simple / Antígeno CTLA-4 / Receptor de Muerte Celular Programada 1 Tipo de estudio: Estudio de casos y controles / Guía de práctica clínica Aspecto clínico: Etiología / Terapia Límite: Adolescente / Adulto / Anciano / Femenino / Humanos / Masculino / Media edad / Joven adulto Idioma: Inglés Revista: Br J Haematol Año: 2018 Tipo del documento: Artículo País de afiliación: Japón