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1.
Eur J Haematol ; 2020 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-32003046

RESUMEN

OBJECTIVE: Myelodysplastic syndromes (MDS), caused by various genetic mutations in hematopoietic stem cells, are associated with highly variable outcomes. Poly (ADP-ribose) polymerase-1 (PARP1) plays an important role in DNA damage repair and contributes to the progression of several types of cancer. Here, we investigated the impact of PARP1 V762A polymorphism on the susceptibility to and prognosis of MDS. METHODS: Samples collected from 105 MDS patients and 202 race-matched healthy controls were subjected to polymerase chain reaction-restriction fragment length polymorphism for genotyping. RESULTS: The allele and genotype frequencies of PARP1 V762A did not differ between MDS patients and the control group. However, MDS patients with the PARP1 V762A non-AA genotype, which is associated with high gene activity, had shorter overall survival rates (P = 0.01) than those with the AA genotype. Multivariate analysis of overall survival also revealed PARP1 V762A non-AA genotype as a poor prognostic factor (P = 0.02). When patients were analyzed according to treatment history, the PARP1 V762A non-AA genotype was only associated with poor survival in patients who had received treatment (P = 0.02). CONCLUSION: PARP1 V762A polymorphism may be an independent prognostic factor for MDS, and a predictive biomarker for MDS treatment.

2.
Clin Exp Med ; 2019 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-31620907

RESUMEN

Single-nucleotide polymorphisms (SNPs) of the programmed cell death protein-1 (PDCD1), programmed cell death protein-1 ligand-1 (PDCD1LG1), and cytotoxic T lymphocyte-associated antigen-4 (CTLA4) genes are implicated in the pathogenesis of some cancers. We investigated the role of PDCD1, PDCD1LG1, and CTLA4 SNPs in MM pathogenesis and the susceptibility to and clinical features of multiple myeloma (MM). We obtained genomic DNA from 124 patients with MM and 211 healthy controls and detected PDCD1 (rs36084323, rs41386349, and rs2227982), PDCD1LG1 (rs2297136 and rs4143815), and CTLA4 (rs733618, rs11571316, rs231775, and rs3087243) genotypes using the polymerase chain reaction-restriction fragment length polymorphism method or the TaqMan allelic discrimination real-time PCR method. The patients with MM had a significantly higher frequency of the PDCD1 GCC/GCC haplotype (rs36084323/rs41386349/rs2227982) compared with the healthy controls. PDCD1 rs2227982 CC genotype was associated significantly with a higher frequency of bone lesions. Patients with PDCD1LG1 rs2297136 TT and TC types (high-expression types) showed lower albumin level than those with CC genotype. In addition, the PDCD1LG1 rs4143815 CC and CG types (high-expression types) were associated significantly with higher frequency of patients who were treated with thalidomide and/or bortezomib. However, there was no statistical significance between CTLA4 polymorphisms and clinical variables of patients with MM. There were no significant differences between all the polymorphisms and OS. Our study indicates that the PDCD1 haplotype is associated with a susceptibility to MM. The PDCD1 rs2227982 and PDCD1LG1 rs2297136 affect the clinical features of multiple myeloma patients.

4.
Int J Hematol ; 109(4): 409-417, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30701467

RESUMEN

A prospective, multicenter, phase II study was performed to assess the efficacy and safety of thalidomide maintenance therapy at different doses in Japanese multiple myeloma (MM) patients. This study included 34 patients (median age, 74 years) who were previously treated with not more than three prior therapies and whose response status was evaluated as at least stable disease. They were randomized into Group A (no maintenance; 12 patients), Group B (50 mg thalidomide maintenance; 12 patients), and Group C (100 mg thalidomide maintenance; 10 patients), respectively. Thalidomide maintenance therapy resulted in improved depth of response in three cases (13.6%) and sustained response after induction therapy in eight cases (36.4%). Two-year progression-free survival (PFS) was 25.0%, 33.3%, and 77.8% in Groups A, B, and C, respectively, and was significantly higher in Group C than in Group A (p = 0.005). There was no difference in the incidence of hematological or non-hematological adverse events between Groups B and C. The current study demonstrates that maintenance with daily thalidomide at 100 mg, but not 50 mg, improved depth of response and prolonged PFS, and that this treatment was feasible for use in Japanese MM patients.


Asunto(s)
Quimioterapia de Mantención , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/mortalidad , Talidomida/administración & dosificación , Grupo de Ascendencia Continental Asiática , Supervivencia sin Enfermedad , Humanos , Japón , Estudios Prospectivos , Tasa de Supervivencia , Talidomida/efectos adversos
5.
Hematol Oncol ; 36(5): 792-800, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30176173

RESUMEN

The international staging system (ISS) is the most commonly used risk-stratification system for patients with multiple myeloma (MM) and is determined by serum albumin and ß2-microglobulin levels. In the two determinants, ß2-microglobulin levels are frequently observed to be elevated in patients with myeloma, particularly in those with renal impairment. In comparison with patients with intact immunoglobulin myeloma, patients with LC myeloma do not necessarily show decreased levels of serum albumin. The clinical impact of ISS in patients with LCMM, in particular the distinction between ISS I and II, may be complicated due to non-decreased levels of serum albumin in both stages. Accordingly, we have attempted to assess clinical relevance of the ISS in patients with LC myeloma. The clinical data of 1899 patients with MM diagnosed between January 2001 and December 2012 were collected from 38 affiliated hospitals of the Japanese Society of Myeloma. Significant difference was not found between stage I (n = 72) and stage II (n = 92) in LC myeloma patients (n = 307). The mean serum albumin concentration of patients with LC myeloma was within the reference range but higher than that of patients with IgG + IgA myeloma (n = 1501), which complicates the distinction between ISS stage I and II myeloma. Patients with LC myeloma had low frequencies of t(4; 14) and high frequency of elevated lactate dehydrogenase, and despite a relevant amount of missing data in our registry (R-ISS stage I; n = 11, stage II; n = 32, and stage III: n = 18), the information included in the R-ISS scoring system seems to be more accurate than ISS to obtain a reliable risk stratification approach in non-ISS stage III LC myeloma patients.


Asunto(s)
Inmunoglobulina A/sangre , Inmunoglobulina G/sangre , Cadenas Ligeras de Inmunoglobulina/sangre , Mieloma Múltiple/sangre , Mieloma Múltiple/patología , Albúmina Sérica Humana/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias
6.
Int J Hematol ; 108(3): 246-253, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-29737460

RESUMEN

Recent studies have shown that tumors of relapsed acute myeloid leukemia (AML) present additional genetic mutations compared to the primary tumors. The base excision repair (BER) pathway corrects oxidatively damaged mutagenic bases and plays an important role in maintaining genetic stability. The purpose of the present study was to investigate the relationship between BER functional polymorphisms and AML relapse. We focused on five major polymorphisms: OGG1 S326C, MUTYH Q324H, APE1 D148E, XRCC1 R194W, and XRCC1 R399Q. Ninety-four adults with AML who achieved first complete remission were recruited. Genotyping was performed with the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The OGG1 S326C CC genotype (associated with lower OGG1 activity) was observed more frequently in patients with AML relapse [28.9 vs. 8.9%, odds ratio (OR) = 4.10, 95% confidence interval (CI) = 1.35-12.70, P = 0.01]. Patients with the CC genotype exhibited shorter relapse-free survival (RFS). Moreover, the TCGA database suggested that low OGG1 expression in AML cells is associated with a higher frequency of mutations. The present findings suggest that the OGG1 S326C polymorphism increased the probability of AML relapse and may be useful as a prognostic factor for AML relapse risk.


Asunto(s)
ADN Glicosilasas/genética , Reparación del ADN/genética , Reparación del ADN/fisiología , Estudios de Asociación Genética , Genotipo , Leucemia Mieloide Aguda/genética , Mutación , Polimorfismo Genético , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Daño del ADN , Supervivencia sin Enfermedad , Femenino , Expresión Génica , Humanos , Leucemia Mieloide Aguda/mortalidad , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Pronóstico , Especies Reactivas de Oxígeno , Recurrencia , Riesgo , Tasa de Supervivencia , Adulto Joven
7.
Transfus Apher Sci ; 57(2): 208-214, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29439918

RESUMEN

OBJECTIVES: There are conflicting results on the influence of recombinant human erythropoietin (rHuEPO) administration to lymphocytes, especially to B cells. METHODS: We analyzed peripheral white blood cell (WBC) subsets in patients who received one bolus administration of rHuEPO. 119 autologous blood donors were enrolled in this study. Fourty-nine out of them were treated with rHuEPO. Blood samples were obtained before the first phlebotomy and one week later before the second one. By flow cytometry, we measured the numbers of WBC, lymphocytes, dendritic cells, CD4+ T cells, CD8+ T cells, natural killer (NK) cells, B cells, monocytes, and neutrophils, further details of B cell subsets. RESULTS: In the EPO-treatment group, absolute numbers of lymphocytes, especially CD8+ T cells, NK cells, and B cells, significantly decreased after rHuEPO administration. In B cell subsets, absolute numbers of naïve B cells and IgD-CD27- B cells significantly decreased. Other B cell subsets, such as transitional B cells, memory B cells, and marginal zone B cells, also showed a decreasing trend. CONCLUSION: These findings suggest that a single administration of rHuEPO can influence human immune system via reduction of B cell number in peripheral blood.


Asunto(s)
Linfocitos B/metabolismo , Eritropoyetina/uso terapéutico , Inmunomodulación/inmunología , Eritropoyetina/farmacología , Femenino , Humanos , Masculino
8.
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
9.
Hematol Oncol ; 36(1): 196-201, 2018 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-28786198

RESUMEN

Single nucleotide polymorphisms (SNPs) in interleukin 17 (IL17A) and IL-23 receptor (IL23R) are involved in the pathogenesis of many cancers and autoimmune diseases. We investigated the influence of IL17A and IL23R SNPs on the risk of developing multiple myeloma (MM) and its clinical features. We obtained genomic DNA from 120 patients with MM and 201 healthy controls and detected IL17A -197 G/A (rs2275913) and IL23R H3Q (rs1884444) genotypes using the polymerase chain reaction-restriction fragment length polymorphism method. There were no significant differences in the genotype and allele frequencies of IL17A -197 G/A and IL23R H3Q between the controls and patients with MM. Compared with the GG and GA genotypes, the IL17A AA genotype was significantly associated with lower hemoglobin levels. The IL23R HH genotype was significantly associated with higher frequency of bone lesions and plasmacytoma than the HQ and QQ genotypes. We observed significant differences in overall survival (OS) between patients treated with thalidomide and/or bortezomib and those treated conventionally. Therefore, we also examined the effect of IL17A and IL23R polymorphisms on the clinical variables and OS in patients treated with thalidomide and/or bortezomib. We observed that the IL23R HH genotype was significantly associated with poor survival compared with the QH and HH genotypes in these patients. Our findings indicate that IL17A -197 G/A and IL23R H3Q are not associated with susceptibility to MM. However, IL-17 and IL-23R polymorphisms may affect severity, bone lesions, and extra-medullary disease in patients with MM. Moreover, IL23R polymorphisms may contribute to poor prognosis in patients with MM treated with thalidomide and/or bortezomib.


Asunto(s)
Interleucina-17/genética , Mieloma Múltiple/genética , Receptores de Interleucina/genética , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/mortalidad , Mieloma Múltiple/patología , Polimorfismo de Nucleótido Simple , Pronóstico , Análisis de Supervivencia
10.
Oncol Lett ; 14(4): 4372-4378, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28943951

RESUMEN

The putative tumor suppressor gene WW domain containing oxidoreductase (WWOX) spans a common fragile site (CFS) on chromosome 16q23.3. CFSs are regions of profound genomic instability and sites for genomic deletions in cancer cells. Therefore, WWOX is structurally altered in diverse nonhematological cancer types. However, the function of WWOX in hematological tumor types, including multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS) remains unclear. WWOX expression and methylation in patients with MM, MGUS, or noninvasive lymphoma (control) were analyzed using reverse transcription- and methylation specific-polymerase chain reaction analysis. Variant WWOX transcripts were detected in 65 and 50% of patients with MM and MGUS, respectively, compared with 10% of controls. WWOX expression was higher in patients with MM, and WWOX promoter methylation was detected in 35% of patients with MM compared with 5% of patients with MGUS and 4% of controls. WWOX promoter methylation was significantly associated with shorter overall survival time of patients, in particular those with MM who were never treated with novel agents. Genomic alterations, including deletions and promoter methylation that affect WWOX expression occur early and may be involved in the pathogenesis, progression, and prognosis of MM.

11.
Br J Haematol ; 179(3): 449-460, 2017 11.
Artículo en Inglés | MEDLINE | ID: mdl-28770558

RESUMEN

Extramedullary myeloma (EMM) occurs when myeloma develops outside the bone marrow; it often develops after chemotherapy and is associated with the acquisition of chemo-resistance and a fatal course. The mechanisms underlying extramedullary spread have not yet been fully elucidated. MALAT1 is a highly abundantly and ubiquitously expressed long non-coding RNA that plays important roles in cancer metastasis. The aims of this study were to clarify the association of MALAT1 with EMM and to elucidate the underlying mechanism of EMM formation under chemotherapeutic pressure. MALAT1 expression was significantly higher in multiple myeloma (MM) than in monoclonal gammopathy of undetermined significance. Furthermore, MALAT1 expression was markedly higher in EMM compared with that in corresponding intramedullary myeloma cells. A higher MALAT1 level was associated with shorter overall and progression-free survival. MALAT1 expression level was positively correlated with expression of HSP90AA1, HSP90AB1 and HSP90B1 but not with TP53 expression. MALAT1 was significantly upregulated by bortezomib and doxorubicin. Considering the known functions of MALAT1, our results suggest that it acts as a stress response gene that is upregulated by chemotherapy, thereby linking chemotherapy to EMM formation. Elucidating the biological implication of long non-coding RNA contributes to deeper understanding concerning the pathogenesis and investigation of novel therapeutic targets for MM.


Asunto(s)
Biomarcadores de Tumor/genética , Mieloma Múltiple/patología , ARN Largo no Codificante/genética , Antineoplásicos/farmacología , Biomarcadores de Tumor/metabolismo , Bortezomib/farmacología , Progresión de la Enfermedad , Doxorrubicina/farmacología , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Masculino , Gammopatía Monoclonal de Relevancia Indeterminada/genética , Gammopatía Monoclonal de Relevancia Indeterminada/metabolismo , Mieloma Múltiple/genética , Pronóstico , ARN Largo no Codificante/biosíntesis , ARN Neoplásico/biosíntesis , ARN Neoplásico/genética , Estrés Fisiológico/genética , Análisis de Supervivencia , Células Tumorales Cultivadas
12.
BMC Immunol ; 18(1): 26, 2017 05 16.
Artículo en Inglés | MEDLINE | ID: mdl-28511637

RESUMEN

BACKGROUND: T-helper cell type 1 (Th1) polarization in chronic immune thrombocytopenia (cITP) has been reported at the protein and mRNA levels. We evaluated the impact of Th1/Th2 cytokine and cytokine receptor functional polymorphisms on both susceptibility to, and severity of, cITP. We analysed IFN-γ + 874 T/A, IFN-γR -611G/A, IL-4 -590C/T, and IL-4Rα Q576R polymorphisms in 126 cITP patients (male/female: 34/92; median age: 47.7 years) and 202 healthy control donors. Genotyping was determined by PCR and direct sequencing. The Th1/Th2 ratio was detected in peripheral blood mononuclear cells via flow cytometry. RESULTS: cITP patients had a higher frequency of the IL-4Rα 576 non-QQ genotype compared to healthy subjects (P = 0.04). cITP patients with the IFN-γ +874 non-AA genotype (high expression type) showed more severe thrombocytopenia than those with the AA genotype (P < 0.05). cITP patients had a significantly higher Th1/Th2 ratio than control patients (P < 0.01); this ratio was inversely correlated with platelet counts. Furthermore, patients with both IFN-γ +874 non-AA genotype (high expression type) and IFN-γR -611 non-AA genotype (high-function type) had a significantly higher Th1/Th2 ratio (P < 0.05). CONCLUSIONS: The cytokine polymorphisms affecting Th1/Th2 increase the susceptibility to, and severity of, chronic ITP.


Asunto(s)
Interferón gamma/genética , Subunidad alfa del Receptor de Interleucina-4/genética , Interleucina-4/genética , Púrpura Trombocitopénica Idiopática/genética , Receptores de Interferón/genética , Células TH1/inmunología , Células Th2/inmunología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Células Cultivadas , Niño , Preescolar , Enfermedad Crónica , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Interferón gamma/metabolismo , Interleucina-4/metabolismo , Subunidad alfa del Receptor de Interleucina-4/metabolismo , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Púrpura Trombocitopénica Idiopática/inmunología , Receptores de Interferón/metabolismo , Balance Th1 - Th2/genética , Adulto Joven
13.
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
15.
Eur J Haematol ; 96(3): 245-51, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25941112

RESUMEN

Polymorphisms of the interleukin-10 (IL-10) gene, which alter the production of IL-10, have been implicated in many cancers. We investigated the association between gene polymorphisms of the promoter region of IL-10 (-1082 G/A, IL-10-819 C/T, and -592 C/A) and the risk to develop myelodysplastic syndrome (MDS) and clinical features of MDS. Genomic DNA was extracted from 119 patients with MDS or chronic myelomonocytic leukemia and 202 healthy controls. Genotypes were determined by PCR-restriction fragment length polymorphism. There were no statistically significant differences in the genotype, allele, and haplotype frequencies of IL-10 -1082 G/A, IL-10-819 C/T, and -592 C/A between the patients with MDS and the control group. However, the IL-10 -592 CC genotype group (IL-10 high producer type) was associated with lower hemoglobin level (7.85 ± 2.02 g/dL vs. 9.37 ± 2.25 g/dL, P = 0.027) and poorer prognosis as compared to the IL-10 -592 non-CC genotype group (median survival time 50.2 m vs. not reached, p = 0.026). In addition, the IL-10 high producer haplotype group (GCC/ACC or ACC/ACC) was also associated with lower hemoglobin level and shorter survival time. Our findings indicate that IL-10 gene polymorphisms may not contribute to susceptibility to MDS, but they may be associated with the severity and prognosis of MDS.


Asunto(s)
Interleucina-10/genética , Síndromes Mielodisplásicos/diagnóstico , Síndromes Mielodisplásicos/genética , Polimorfismo de Nucleótido Simple , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Genotipo , Haplotipos , Humanos , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/mortalidad , Síndromes Mielodisplásicos/terapia , Oportunidad Relativa , Regiones Promotoras Genéticas , Modelos de Riesgos Proporcionales , Adulto Joven
16.
Rinsho Byori ; 63(3): 305-11, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26524852

RESUMEN

BACKGROUND: Hepatitis B virus (HBV) and hepatitis C virus (HCV) are important human pathogens that cause chronic liver disease and hepatocellular carcinoma. Co-infection of HBV and HCV is not uncommon, particularly in countries where these two viruses are endemic. Therefore, the characteristics of HBV co-infection in HCV antibody (HCVAb) -positive Japanese patients found on the screening examination were analyzed. PATIENTS AND METHODS: Between January and December 2011, HCVAb status was evaluated as the screening examination in 12,582 patients in Gunma University Hospital, and it was positive in 402 patients (3.2%). In 331 HCVAb-positive/HBs antigen (HBsAg) -negative patients with available residual serum, HBs antibody (HBsAb) and HBc antibody (HBcAb) were examined. In addition, HCV-RNA was examined in 291 patients with available residual serum. HBV-DNA and HBV core-related antigen (HBcrAg) were examined in 106 patients with available residual serum. RESULTS: The HCVAb titer was distributed between 1 and 18 sample/cutoff index (S/CO). 275 patients (83.1%) had a high HCVAb titer (S/CO ≥10). HCV-RNA was positive in 230 (79.0%) patients, and it was more frequently detected in HCVAb high-titer patients (88%) than in low-titer patients (32%; p < 0.0001); 61 (18.4%) and 101(30.5%) patients were positive for HBsAb and HBcAb, respectively. Of 230 HCV-RNA-positive patients, 38 (16.5%) and 59 (25.6%) were positive for HBsAb and HBcAb, respectively. Three (2.8%) and 2 (1.9%) of 106 patients had HBV-DNA and HBVCrAg. The ALT level was higher than 30 IU/L in 146/327 (44.6%) HCVAb-positive patients who had ALT levels measured. Abnormal ALT elevation was more frequent in HCVAb high-titer patients than in low-titer patients (48.3% vs. 26.8%; p = 0.0031), and in HCV-RNA-positive patients than in HCV-RNA-negative patients (54.2% vs. 13.3%; p < 0.001). CONCLUSION: HBV reactivation should be noted in these HCVAb-positive/HBsAg-negative patients on the screening examination if these patients must receive chemotherapy or immunosuppressive therapy. In addition, surveying of HBsAb in addition to HBcAb is also necessary.


Asunto(s)
Coinfección/diagnóstico , Anticuerpos contra la Hepatitis B/sangre , Antígenos del Núcleo de la Hepatitis B/inmunología , Antígenos de Superficie de la Hepatitis B/inmunología , Hepatitis B/diagnóstico , Hepatitis C/diagnóstico , Tamizaje Masivo/métodos , Adulto , Anciano , Anciano de 80 o más Años , Grupo de Ascendencia Continental Asiática , Biomarcadores/sangre , Coinfección/epidemiología , Coinfección/prevención & control , Femenino , Hepatitis B/epidemiología , Hepatitis B/prevención & control , Hepatitis C/epidemiología , Hepatitis C/prevención & control , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Adulto Joven
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