ATP5H/KCTD2 locus is associated with Alzheimer's disease risk.

To identify loci associated with Alzheimer disease, we conducted a three-stage analysis using existing genome-wide association studies (GWAS) and genotyping in a new sample. In Stage I, all suggestive single-nucleotide polymorphisms (at P<0.001) in a previously reported GWAS of seven independent studies (8082 Alzheimer's disease (AD) cases; 12 040 controls) were selected, and in Stage II these were examined in an in silico analysis within the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium GWAS (1367 cases and 12904 controls). Six novel signals reaching P<5 × 10(-6) were genotyped in an independent Stage III sample (the Fundació ACE data set) of 2200 sporadic AD patients and 2301 controls. We identified a novel association with AD in the adenosine triphosphate (ATP) synthase, H+ transporting, mitochondrial F0 (ATP5H)/Potassium channel tetramerization domain-containing protein 2 (KCTD2) locus, which reached genome-wide significance in the combined discovery and genotyping sample (rs11870474, odds ratio (OR)=1.58, P=2.6 × 10(-7) in discovery and OR=1.43, P=0.004 in Fundació ACE data set; combined OR=1.53, P=4.7 × 10(-9)). This ATP5H/KCTD2 locus has an important function in mitochondrial energy production and neuronal hyperpolarization during cellular stress conditions, such as hypoxia or glucose deprivation.

[Treatment of indolent non-Hodgkin's lymphomas]. / Tratamiento de los linfomas no hodgkinianos indolentes.

Non-Hodgkin's Lymphomas (NHLs) are a heterogeneous group of entities with different pathologies. A total of 80% of these lymphomas are B-cell origin and only 20% T-cell. B-cell lymphomas express CD-20 antigen, a specific target for the current treatment with monoclonal antibodies. Indolent lymphomas in localized stages (I and II) account for 20%, only 10% being in pathological stages. The possibilities for cure with radiotherapy and/or chemotherapy are approximately 50-70%. Advanced stages (IIB, III and IV) of phenotype B types account for 80-90% of the cases and are candidates for systemic treatments with immunochemotherapy for those of phenotype B. Rescue treatment is one of the most important problems in this type of lymphomas, many of them needing second line treatments, with survival rates under five years, in spite of the 50% response rate. In these cases, immunochemotherapy includes more aggressive regimens, high-dose chemotherapy and combined chemoimmunoradiotherapy.

Tratamiento de los linfomas no hodgkinianos indolentes / Treatment of indolent non-Hodgkin’s Lymphomas

Los linfomas no hodgkinianos (LNH) son un conjunto muy heterogéneo de procesos con distintas características clínicas y anatomopatológicas. El 80% de estos linfomas son de origen B y sólo un 20% T. Los B expresan el antígeno CD20, una diana clave para el tratamiento actual con anticuerpos monoclonales. En el grupo de linfomas indolentes, los estadios clínicos localizados (estadios I y II) representan el 20%, siendo sólo estadios patológicos un 10%. Las posibilidades de curación se sitúan en un 50-70% con radioterapia y/o quimioterapia. Los estadios avanzados III-IV, incluyendo el IIB, representan el 80-90% de los casos y son candidatos a tratamientos sistémicos con inmunoquimioterapia para los de fenotipo B. El tratamiento de rescate es uno de los problemas más importantes en estos linfomas, muchos requieren tratamiento de segunda línea, con supervivencias inferiores a cinco años, a pesar del 50% de respuestas. Contempla protocolos más agresivos de inmunoquimioterapia, incluyendo las altas dosis y radioinmunoquimioterapia (AU)

Non-Hodgkin’s Lymphomas (NHLs) are a heterogeneous group of entities with different pathologies. A total of 80% of these lymphomas are B-cell origin and only 20% T-cell. B-cell lymphomas express CD-20 antigen, a specific target for the current treatment with monoclonal antibodies. Indolent lymphomas in localized stages (I and II) account for 20%, only 10% being in pathological stages. The possibilities for cure with radiotherapy and/or chemotherapy are approximately 50-70%. Advanced stages (IIB, III and IV) of phenotype B types account for 80-90% of the cases and are candidates for systemic treatments with immunochemotherapy for those of phenotype B. Rescue treatment is one of the most important problems in this type of lymphomas, many of them needing second line treatments, with survival rates under five years, in spite of the 50% response rate. In these cases, immunochemotherapy includes more aggressive regimens, high-dose chemotherapy and combined chemoim-munoradiotherapy (AU)