Association between IL-18 gene polymorphisms and biopsy-proven giant cell

INTRODUCTION: The objective was to investigate the potential implication of the IL18 gene promoter polymorphisms in the susceptibility to giant-cell arteritis GCA). METHODS: In total, 212 patients diagnosed with biopsy-proven GCA were included in this study. DNA from patients and matched controls was obtained from peripheral blood. Samples were genotyped for the IL18-137 G>C (rs187238), the IL18-607 C>A (rs1946518), and the IL18-1297 T>C (rs360719) gene polymorphisms with polymerase chain reaction, by using a predesigned TaqMan allele discrimination assay. RESULTS: No significant association between the IL18-137 G>C polymorphism and GCA was found. However, the IL18 -607 allele A was significantly increased in GCA patients compared with controls (47.8% versus 40.9% in patients and controls respectively; P = 0.02; OR, 1.32; 95% CI, 1.04 to 1.69). It was due to an increased frequency of homozygosity for the IL18 -607 A/A genotype in patients with GCA (20.4%) compared with controls (13.4%) (IL18 -607 A/A versus IL18 -607 A/C plus IL18 -607 C/C genotypes: P = 0.04; OR, 1.59; 95% CI, 1.02 to 2.46). Also, the IL18-1297 allele C was significantly increased in GCA patients (30.7%) compared with controls (23.0%) (P = 0.003; OR, 1.48; 95% CI, 1.13 to 1.95). In this regard, an increased susceptibility to GCA was observed in individuals carrying the IL18-1297 C/C or the IL18-1297 C/T genotypes compared with those carrying the IL18-1297 T/T genotype (IL18-1297 C/C plus IL18-1297 T/C versus IL18-1297 T/T genotype in GCA patients compared with controls: P = 0.005; OR, 1.61; 95% CI, 1.15 to 2.25). We also found an additive effect of the IL18 -1297 and -607 polymorphisms with TLR4 Asp299Gly polymorphism. The OR for GCA was 1.95 for combinations of genotypes with one or two risk alleles, whereas carriers of three or more risk alleles have an OR of 3.7. CONCLUSIONS: Our results show for the first time an implication of IL18 gene-promoter polymorphisms in the susceptibility to biopsy-proven GCA. In addition, an additive effect between the associated IL18 and TLR4 genetic variants was observed.

Multiple sclerosis risk variant HLA-DRB1*1501 associates with high expression of DRB1 gene in different human populations.

The human leukocyte antigen (HLA) DRB1*1501 has been consistently associated with multiple sclerosis (MS) in nearly all populations tested. This points to a specific antigen presentation as the pathogenic mechanism though this does not fully explain the disease association. The identification of expression quantitative trait loci (eQTL) for genes in the HLA locus poses the question of the role of gene expression in MS susceptibility. We analyzed the eQTLs in the HLA region with respect to MS-associated HLA-variants obtained from genome-wide association studies (GWAS). We found that the Tag of DRB1*1501, rs3135388 A allele, correlated with high expression of DRB1, DRB5 and DQB1 genes in a Caucasian population. In quantitative terms, the MS-risk AA genotype carriers of rs3135388 were associated with 15.7-, 5.2- and 8.3-fold higher expression of DQB1, DRB5 and DRB1, respectively, than the non-risk GG carriers. The haplotype analysis of expression-associated variants in a Spanish MS cohort revealed that high expression of DRB1 and DQB1 alone did not contribute to the disease. However, in Caucasian, Asian and African American populations, the DRB1*1501 allele was always highly expressed. In other immune related diseases such as type 1 diabetes, inflammatory bowel disease, ulcerative colitis, asthma and IgA deficiency, the best GWAS-associated HLA SNPs were also eQTLs for different HLA Class II genes. Our data suggest that the DR/DQ expression levels, together with specific structural properties of alleles, seem to be the causal effect in MS and in other immunopathologies rather than specific antigen presentation alone.

Genome-wide association study of multiple sclerosis confirms a novel locus at 5p13.1.

Multiple Sclerosis (MS) is the most common progressive and disabling neurological condition affecting young adults in the world today. From a genetic point of view, MS is a complex disorder resulting from the combination of genetic and non-genetic factors. We aimed to identify previously unidentified loci conducting a new GWAS of Multiple Sclerosis (MS) in a sample of 296 MS cases and 801 controls from the Spanish population. Meta-analysis of our data in combination with previous GWAS was done. A total of 17 GWAS-significant SNPs, corresponding to three different loci were identified:HLA, IL2RA, and 5p13.1. All three have been previously reported as GWAS-significant. We confirmed our observation in 5p13.1 for rs9292777 using two additional independent Spanish samples to make a total of 4912 MS cases and 7498 controls (ORpooled = 0.84; 95%CI: 0.80-0.89; p = 1.36 × 10-9). This SNP differs from the one reported within this locus in a recent GWAS. Although it is unclear whether both signals are tapping the same genetic association, it seems clear that this locus plays an important role in the pathogenesis of MS.

IL2RA/CD25 gene polymorphisms: uneven association with multiple sclerosis (MS) and type 1 diabetes (T1D).

BACKGROUND: IL-2 receptor (IL2R) alpha is the specific component of the high affinity IL2R system involved in the immune response and in the control of autoimmunity. METHODS AND RESULTS: Here we perform a replication and fine mapping of the IL2RA gene region analyzing 3 SNPs previously associated with multiple sclerosis (MS) and 5 SNPs associated with type 1 diabetes (T1D) in a collection of 798 MS patients and 927 matched Caucasian controls from the south of Spain. We observed association with MS in 6 of 8 SNPs. The rs1570538, at the 3'- UTR extreme of the gene, previously reported to have a weak association with MS, is replicated here (P = 0.032). The most associated T1D SNP (rs41295061) was not associated with MS in the present study. However, the rs35285258, belonging to another independent group of SNPs associated with T1D, showed the maximal association in this study but different risk allele. We replicated the association of only one (rs2104286) of the two IL2RA SNPs identified in the recently performed genome-wide association study of MS. CONCLUSIONS: These findings confirm and extend the association of this gene with MS and reveal a genetic heterogeneity of the associated polymorphisms and risk alleles between MS and T1D suggesting different immunopathological roles of IL2RA in these two diseases.

Evidence of new risk genetic factor to systemic lupus erythematosus: the UBASH3A gene

The ubiquitin associated and Src-homology 3 (SH3) domain containing A (UBASH3a) is a suppressor of T-cell receptor signaling, underscoring antigen presentation to T-cells as a critical shared mechanism of diseases pathogenesis. The aim of the present study was to determine whether the UBASH3a gene influence the susceptibility to systemic lupus erythematosus (SLE) in Caucasian populations. We evaluated five UBASH3a polymorphisms (rs2277798, rs2277800, rs9976767, rs13048049 and rs17114930), using TaqMan® allelic discrimination assays, in a discovery cohort that included 906 SLE patients and 1165 healthy controls from Spain. The SNPs that exhibit statistical significance difference were evaluated in a German replication cohort of 360 SLE patients and 379 healthy controls. The case-control analysis in the Spanish population showed a significant association between the rs9976767 and SLE (Pc = 9.9E-03 OR = 1.21 95%CI = 1.07-1.37) and a trend of association for the rs2277798 analysis (P = 0.09 OR = 0.9 95%CI = 0.79-1.02). The replication in a German cohort and the meta-analysis confirmed that the rs9976767 (Pc = 0.02; Pc = 2.4E-04, for German cohort and meta-analysis, respectively) and rs2277798 (Pc = 0.013; Pc = 4.7E-03, for German cohort and meta-analysis, respectively) UBASH3a variants are susceptibility factors for SLE. Finally, a conditional regression analysis suggested that the most likely genetic variation responsible for the association was the rs9976767 polymorphism. Our results suggest that UBASH3a gene plays a role in the susceptibility to SLE. Moreover, our study indicates that UBASH3a can be considered as a common genetic factor in autoimmune diseases.

The systemic lupus erythematosus IRF5 risk haplotype is associated with systemic sclerosis

Systemic sclerosis (SSc) is a fibrotic autoimmune disease in which the genetic component plays an important role. One of the strongest SSc association signals outside the human leukocyte antigen (HLA) region corresponds to interferon (IFN) regulatory factor 5 (IRF5), a major regulator of the type I IFN pathway. In this study we aimed to evaluate whether three different haplotypic blocks within this locus, which have been shown to alter the protein function influencing systemic lupus erythematosus (SLE) susceptibility, are involved in SSc susceptibility and clinical phenotypes. For that purpose, we genotyped one representative single-nucleotide polymorphism (SNP) of each block (rs10488631, rs2004640, and rs4728142) in a total of 3,361 SSc patients and 4,012 unaffected controls of Caucasian origin from Spain, Germany, The Netherlands, Italy and United Kingdom. A meta-analysis of the allele frequencies was performed to analyse the overall effect of these IRF5 genetic variants on SSc. Allelic combination and dependency tests were also carried out. The three SNPs showed strong associations with the global disease (rs4728142: P  = 1.34×10(-8), OR  = 1.22, CI 95%  = 1.14-1.30; rs2004640: P  = 4.60×10(-7), OR  = 0.84, CI 95%  = 0.78-0.90; rs10488631: P  = 7.53×10(-20), OR  = 1.63, CI 95%  = 1.47-1.81). However, the association of rs2004640 with SSc was not independent of rs4728142 (conditioned P  = 0.598). The haplotype containing the risk alleles (rs4728142*A-rs2004640*T-rs10488631*C: P  = 9.04×10(-22), OR  = 1.75, CI 95%  = 1.56-1.97) better explained the observed association (likelihood P-value  = 1.48×10(-4)), suggesting an additive effect of the three haplotypic blocks. No statistical significance was observed in the comparisons amongst SSc patients with and without the main clinical characteristics. Our data clearly indicate that the SLE risk haplotype also influences SSc predisposition, and that this association is not sub-phenotype-specific.

Two functional variants of IRF5 influence the development of macular edema in patients with non-anterior uveitis.

OBJECTIVE Interferon (IFN) signaling plays a crucial role in autoimmunity. Genetic variation in interferon regulatory factor 5 (IRF5), a major regulator of the type I interferon induction, has been associated with risk of developing several autoimmune diseases. In the current study we aimed to evaluate whether three sets of correlated IRF5 genetic variants, independently associated with SLE and with different functional roles, are involved in uveitis susceptibility and its clinical subphenotypes. METHODS Three IRF5 polymorphisms, rs2004640, rs2070197 and rs10954213, representative of each group, were genotyped using TaqMan® allelic discrimination assays in a total of 263 non-anterior uveitis patients and 724 healthy controls of Spanish origin. RESULTS A clear association between two of the three analyzed genetic variants, rs2004640 and rs10954213, and the absence of macular edema was observed in the case/control analysis (P FDR =5.07E-03, OR=1.48, CI 95%=1.14-1.92 and P FDR =3.37E-03, OR=1.54, CI 95%=1.19-2.01, respectively). Consistently, the subphenotype analysis accordingly with the presence/absence of this clinical condition also reached statistical significance (rs2004640: P=0.037, OR=0.69, CI 95%=0.48-0.98; rs10954213: P=0.030, OR=0.67, CI 95%=0.47-0.96), thus suggesting that both IRF5 genetic variants are specifically associated with the lack of macular edema in uveitis patients. CONCLUSION Our results clearly showed for the first time that two functional genetic variants of IRF5 may play a role in the development of macular edema in non-anterior uveitis patients. Identifying genetic markers for macular edema could lead to the possibility of developing novel treatments or preventive therapies.

Intronic variants in the NFKB1 gene may influence hearing forecast in patients with unilateral sensorineural hearing loss in Meniere's disease.

Meniere's disease is an episodic vestibular syndrome associated with sensorineural hearing loss (SNHL) and tinnitus. Patients with MD have an elevated prevalence of several autoimmune diseases (rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis and psoriasis), which suggests a shared autoimmune background. Functional variants of several genes involved in the NF-κB pathway, such as REL, TNFAIP3, NFKB1 and TNIP1, have been associated with two or more immune-mediated diseases and allelic variations in the TLR10 gene may influence bilateral affectation and clinical course in MD. We have genotyped 716 cases of MD and 1628 controls by using the ImmunoChip, a high-density genotyping array containing 186 autoimmune loci, to explore the association of immune system related-loci with sporadic MD. Although no single nucleotide polymorphism (SNP) reached a genome-wide significant association (p<10(-8)), we selected allelic variants in the NF-kB pathway for further analyses to evaluate the impact of these SNPs in the clinical outcome of MD in our cohort. None of the selected SNPs increased susceptibility for MD in patients with uni or bilateral SNHL. However, two potential regulatory variants in the NFKB1 gene (rs3774937 and rs4648011) were associated with a faster hearing loss progression in patients with unilateral SNHL. So, individuals with unilateral MD carrying the C allele in rs3774937 or G allele in rs4648011 had a shorter mean time to reach hearing stage 3 (>40 dB HL) (log-rank test, corrected p values were p = 0.009 for rs3774937 and p = 0.003 for rs4648011, respectively). No variants influenced hearing in bilateral MD. Our data support that the allelic variants rs3774937 and rs4648011 can modify hearing outcome in patients with MD and unilateral SNHL.

La renta petrolera venezolana como posible factor de desequilibrio en la geopolítica Suramericana

Pocas cosas ocurren en Venezuela que no tengan, directa o indirectamente que ver con el petróleo. Al hablar de este país es necesario referirnos a la condición petrolera de su economía y su sociedad. La aparición del petróleo significó una nueva fuente de producción rentística que no tardaría en ser de gran importancia, ya que este recurso, es uno de los más codiciados combustibles del progreso industrial, que día a día se cotiza dentro de los mercados internacionales a niveles históricos demostrando sus efectos a nivel global. El auge de los precios del petróleo ha generado ingresos sin precedentes para el Gobierno de Venezuela, “brindándole la oportunidad al Presidente Hugo Chávez de aprovecharse de los grandes flujos de petrodólares, no solo para financiar sus ingentes gastos sociales sino también para subvencionar muchos de sus objetivos geopolíticos en el escenario internacional.1 La pregunta que surge ante dichos factores es ¿Como el mapa geopolítico suramericano podría ser modificado por la asignación que el presidente Hugo Chávez Frías le da a los recursos provenientes de la renta petrolera venezolana?

Programa de preparación física para controlar el desequilibrio muscular lumbo-pelvico como factor de riesgo de la pubalgia en los jugadores de la categoría sub 21 del club deportivo los millonarios

El presente trabajo es el resultado de un exhaustivo proceso investigativo a cerca de los factores de riesgo que predisponen al futbolista de alta competencia a padecer una entidad patológica severamente incapacitante como es la Pubalgia, la cual interfiere en el desempeño del mismo. Inicialmente el trabajo se centra en la revisión y comprensión de los conceptos básicos relacionados con salud, perfil del fisioterapeuta, actividad física, altas demandes cinéticas, anatomía y biomecánica normal de la Pélvis y sus alteraciones, definición de la Pubalgia, los principales factores de riesgo tanto intrínsecos como extrínsecos y el manejo médico y fisioterapéutico de esta entidad patológica.

El desequilibrio procesal y probatorio del “opositor víctima o sujeto vulnerable” en el proceso de restitución de tierras

El presente trabajo se enmarca en la Ley de Víctimas, Ley 1448 del año 2011, y aborda específicamente los casos en que se presenta oposición de una víctima o bien de un sujeto vulnerable, de especial protección, frente a la reclamación de restitución de un predio por una víctima. No aborda la generalidad de los casos de oposición. Habiendo delimitado el objeto de estudio que atañe, es necesario señalar que el presente trabajo, se centra en indagar la posición procesal y las capacidades probatorias del opositor víctima o sujeto vulnerable en este tipo de procesos bajo las circunstancias ya enunciadas, para entrar a estudiar si, a este sujeto procesal se le respeta o se le viola su derecho a la igualdad de parte dentro del proceso de restitución de tierras y qué alternativas pueden establecerse para hacer del acto de oponerse un acto más garantista.

Mercado laboral calificado en Colombia: Estudio sobre el desequilibrio entre oferta y demanda de trabajo para los años 2020 y 2030

El propósito básico de esta investigación es identificar los desajustes (déficits o superávits) no estructurales entre la oferta y demanda de trabajo en Colombia para los años 2020 y 2030, así como interpretar los hallazgos y proponer elementos de estrategia para las empresas a fin de mitigar los efectos adversos del desajuste sobre su capacidad para atraer y retener talento. El argumento central del proyecto consiste en sostener que en un escenario no mayor a los 10 años la oferta de trabajo calificado en Colombia no será suficiente para (i) equilibrar el mercado y (ii) atender la demanda agregada de trabajo, debido a los cambios generacionales en la realidad demográfica del país, el bajo nivel de preparación de la fuerza laboral disponible y los altos índices de informalidad de los trabajadores y las empresas. Dentro de los resultados se presenta una proyección del comportamiento del mercado de trabajo, así como la magnitud del desequilibrio entre los agentes del mercado. Este estudio aplicado es una propuesta cuantitativa de aproximación a la crisis de talento que se revisa en otros estudios. Es un precedente sólido para profundizar con otros enfoques el futuro del trabajo en Colombia.

Desequilibrio entre lenguas y rendimiento escolar : el lenguaje como mediador del éxito académico en contextos bilingües.

Analizar el nivel de éxito-fracaso escolar entre alumnos de Aragón y de Asturias que reciben enseñanza exclusivamente en lengua castellana y alumnos a los que se les imparten clases optativas en catalán y en asturiano. En el caso aragonés, los objetivos son: evaluar el conocimiento matemático desarrollado por los escolares catalanoparlantes de Aragón, tomando como referencia el correspondiente a sus coetáneos que habitan en territorios aragoneses monolingües; establecer, en el caso de que hubiese diferencias, los factores (individuales, sociales o del currículum) explicativos de los mismos; orientar, en función de los análisis precedentes y ante perspectivas de cambios a corto plazo, derivados del traspaso de competencias educativas y la implantación de la LOGSE, hacia líneas de actuación educativa más acordes con la naturaleza social bilingüe de la Franja aragonesa. Sus hipótesis son: 1. El alumnado catalanoparlante de Aragón que asiste a clases de catalán, evidencia un conocimiento matemático superior al de sus coetáneos que no asisten a dichas clases. 2. Los escolares del grupo control obtienen resultado aproximados, en cuanto a conocimiento matemático, que los escolares catanoparlantes de Aragón que asisten a clases de lengua catalana. 3. Los escolares del grupo control obtienen resultados superiores, en cuanto a conocimiento matemático, que los escolares catalanoparlantes de Aragón que no asisten a clases de lengua catalana. En el caso asturiano, las hipótesis son: 1. El alumnado asturiano que asiste a clases de lengua asturiana, evidencia un conocimiento de lengua castellana superior al de sus coetáneos que no asisten a dichas clases. 2. El alumnado asturiano que asiste a clases de lengua asturiana, evidencia un conocimiento matemático superior al de sus coetáneos que no asisten a dichas clases. 3. Existirá una correlación positiva entre el conocimeinto lingüístico en castellano y el conocimiento matemático del alumnado. 240 alumnos y alumnas de centros públicos de enseñanza primaria y de segundo de ESO de municipios de la comarca del Bajo Cinca, en el caso aragonés; 231 alumnos y alumnas de 6 centros de enseñanza primaria que imparten el primer ciclo de Secundaria y 8 Institutos de Enseñanza Secundaria, en el caso asturiano. Las variables estudiadas en el caso aragonés fueron: condición lingüística familiar (CLF), opcionalidad (OPC), situación socioprofesional (SSP), cociente intelectual (CI), sector y conocimiento matemático (IAEP); en el caso asturiano, las variables fueron: condición lingüística familiar (CLF), situación socioprofesional (SSP), opcionalidad (OPC), cociente intelectual (CI) y centro. Entre otros, los instrumentos utilizados fueron la evaluación del conocimiento matemático elaborada por la IAEP, y en el caso asturiano además, la evaluación de conocimiento lingüístico castellano. Statview 1.04 y técnicas descriptivas. Los resultados finales muestran que los escolares catalanoparlantes de Aragón que asisten a clases de lengua catalana, al estructurar su propia lengua, obtienen un beneficio añadido en conocimiento de lengua castellana que incide directamente en un mejor rendimiento matemático comparado con aquellos que no asisten a dichas clases. Además, no aparecen diferencias significativas con sus coetáneos que habitan territorios aragoneses monolingües, mientras que sí aparecen entre éstos últimos y los escolares catalanoparlantes que no asisten a clases de lengua catalana. Respecto a la muestra asturiana, los datos ponen de manifiesto una mejora en el conocimiento lingüístico castellano en aquel alumnado que asiste a clases de asturiano. Se observa también una correlación positiva entre conocimiento lingüístico castellano y conocimiento matemático. En cuanto al conocimiento matemático, aparecen diferencias notables entre el alumnado que cursa sus estudios en centros de Primaria y centros de Secundaria, lo que se interpreta en función del pobre estatus del asturiano y la poca tradición en su incorporación como materia del currículum en los IES.

Crecimiento, desequilibrio y disparidades: interpretación del proceso de desarrollo económico

Documento en inglés (88751) y también en portugués: Interpretação do proceso de desenvolvimento econômico da América Latina. Estudos Econômicos, São Paulo, v, 1, No 3-4, p. 271-308, setembro e dezembro 1950; y en Revista Brasileira de Economia, Rio de Janeiro, año 5, No 1, p. 7-135, março 1951, con un resumen en inglés y francés, p. 117-135 (78593); y también en Prebisch, Raúl: Interpretación del proceso de desarrollo latinoamericano en 1949. Santiago, CEPAL, 1973, p. 1-92, Serie conmemorativa del XXV aniversario de la CEPAL, febrero 1973 (8962); y en Gurrieri, Adolfo, comp.: La obra de Prebisch en la CEPAL. México, DF, Fondo de Cultura Económica, 1982, Tomo I, p. 156-247, Lecturas, No 46 (11934), ingresado en Biblioteca

La política económica colombiana en un año de desequilibrio del balance de pagos = Colombia's economic policy in a year of balance-of-payments disequilibrium

Incluye Bibliografía