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1.
Br J Haematol ; 180(5): 705-714, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29359792

RESUMEN

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.


Asunto(s)
Antígeno CTLA-4/genética , Polimorfismo de Nucleótido Simple/genética , Receptor de Muerte Celular Programada 1/genética , Púrpura Trombocitopénica Idiopática/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Enfermedad Crónica , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad/genética , Genotipo , Glucocorticoides/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Prednisolona/uso terapéutico , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Factores de Riesgo , Adulto Joven
2.
Hematol Oncol ; 35(4): 711-718, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27405747

RESUMEN

Interleukin-10 (IL-10) and IL-10 receptor (IL-10R) single nucleotide polymorphisms have been implicated in the pathogenesis of many cancers. We investigated the influence of IL-10 -592C/A, IL-10RA I224V, and IL-10RB K47E on the risk of developing multiple myeloma (MM) and the clinical features of MM. We extracted the genomic DNA from 128 MM patients and 202 healthy controls and used polymerase chain reaction-restriction fragment length polymorphism method to detect IL-10 promoter -592C/A (rs1800872), IL-10RA (rs2228055), and IL-10RB K47E (rs2834167) genotypes. Overall survival (OS) was defined as the interval from the date of diagnosis to the date of death or last clinical appointment. No statistically significant difference was observed in the genotype and allele frequencies of IL-10 -592C/A, IL-10RA I224V, and IL-10RB K47E between MM patients and healthy controls. IL-10RA II genotype was significantly associated with a hemoglobin level lower than that of IV and VV genotypes (mean ± standard deviation, 9.21 ± 2.46 vs 10.3 ± 2.33 g/dL; P = .021). IL-10 -592 AA genotype was significantly associated with OS better than that of CA and CC genotypes (median OS, 74.5 vs 46.3 months; P = .047). We observed significant differences in survival between patients treated with thalidomide and/or bortezomib and those treated with conventional treatments (median OS, 74.5 vs 38.2 months; P = .021). Therefore, we also examined the effect of IL-10 and IL-10R polymorphisms on the clinical variables and OS of patients treated with thalidomide and/or bortezomib. In addition, IL-10RB EE genotype was significantly associated with poorer survival than KK and KE genotypes (median OS, 46.3 vs 78.8 months; P = .015). Our findings indicate that IL-10 and IL-10R gene polymorphisms may not contribute to the susceptibility to MM but may be associated with the severity and prognosis of MM. In particular, IL-10RB K47E polymorphism may contribute to the poor prognosis of MM patients treated with thalidomide and/or bortezomib.


Asunto(s)
Predisposición Genética a la Enfermedad , Subunidad beta del Receptor de Interleucina-10/genética , Mieloma Múltiple/genética , Mieloma Múltiple/mortalidad , Polimorfismo de Nucleótido Simple , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bortezomib/administración & dosificación , Bortezomib/uso terapéutico , Estudios de Casos y Controles , Terapia Combinada , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Interleucina-10/genética , Masculino , Persona de Mediana Edad , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/tratamiento farmacológico , Estadificación de Neoplasias , Pronóstico , Análisis de Supervivencia , Talidomida/administración & dosificación , Talidomida/uso terapéutico
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