Genetically determined Amerindian ancestry correlates with increased frequency of risk alleles for systemic lupus erythematosus

Objective To assess whether genetically determined Amerindian ancestry predicts increased presence of risk alleles of known susceptibility genes for systemic lupus erythematosus (SLE). Methods Single-nucleotide polymorphisms (SNPs) within 16 confirmed genetic susceptibility loci for SLE were genotyped in a set of 804 Mestizo lupus patients and 667 Mestizo healthy controls. In addition, 347 admixture informative markers were genotyped. Individual ancestry proportions were determined using STRUCTURE. Association analysis was performed using PLINK, and correlation between ancestry and the presence of risk alleles was analyzed using linear regression. Results A meta-analysis of the genetic association of the 16 SNPs across populations showed that TNFSF4 , STAT4 , ITGAM , and IRF5 were associated with lupus in a Hispanic Mestizo cohort enriched for European and Amerindian ancestry. In addition, 2 SNPs within the major histocompatibility complex region, previously shown to be associated in a genome-wide association study in Europeans, were also associated in Mestizos. Using linear regression, we predicted an average increase of 2.34 risk alleles when comparing an SLE patient with 100% Amerindian ancestry versus an SLE patient with 0% Amerindian ancestry ( P < 0.0001). SLE patients with 43% more Amerindian ancestry were predicted to carry 1 additional risk allele. Conclusion Our results demonstrate that Amerindian ancestry is associated with an increased number of risk alleles for SLE.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78480/1/27753_ftp.pd

Innovación tecnológica en el ámbito electoral: el caso de la ONPE

This article reviews the most significant technological innovations developed by ONPE in recent years. These innovations were born based on the concepts of process management, results management, competencies management and the Malcolm Bridge performance excellence model implemented at the ONPE in 2014. The technological innovations developed in the institution on the basis of Information and Communication Technologies seek to improve services offered to citizens by following what the excellence in management model establishes. The article reflects that currently each of these technological innovations and their positive effects have yielded a high level of competitiveness in the organization, making it become an example of modernization for other public sector organizations in Perú.En el presente artículo se hace un recuento de las innovaciones tecnológicas más significativas desarrolladas por la ONPE en los últimos años. Tales innovaciones han sido concebidas bajo el enfoque de gestión por procesos, gestión por resultados, gestión de las competencias y el modelo de excelencia en la gestión de Malcolm Baldrige, el cual se viene implementando desde el año 2014 en la ONPE. Las innovaciones tecnológicas basadas en las Tecnologías de la Información y de la Comunicaciones desarrolladas en la institución buscan mejorar los servicios ofrecidos a la ciudadanía, siguiendo lo establecido en el modelo de excelencia de la gestión. El artículo refleja que, en la actualidad, cada una de estas innovaciones tecnológicas y los efectos positivos que han tenido sitúan a la organización en un alto nivel de competitividad, constituyéndose en un ejemplo para la modernización de otros organismos del sector público en el Perú

Biopsia de Grasa Subcutánea para el Diagnóstico de Amiloidosis Secundaria en Artritis Reumatoide

OBJECTIVE: To detect secondary amyloidosis (AA) in patients with rheumatoid arthritis (RA). MATERIAL AND METHODS: We assayed length of disease, extraarticular involvement, functional ability, anatomical compromise, white cell count, erythrocyte sedimentation rate, rheumatoid factor (RF) (latex test), serum albumin, and urine analysis. All of patients underwent periumbilical aspirate of subcutaneous fat. Samples were stained with Congo red, and light microscopy and polarized microscopy were used. Green-apple birefrigence was taken as AA (+). RESULTS: We studied 81 patients with RA (ACR criteria), 71 of them were females. The ages were between 31 and 80 years. 75/81 patients were RF (+), 3/81 were AA (+). Average length of disease was 14,74 years in AA (-) patients and 20,3 years in AA (+). Just one patient showed renal deposits of amyloid. CONCLUSION: Our occurrence of amyloidosis in patients with AR was lower. Patients with secondary amiloidosis and AR had higher RF levels and larger length of disease.OBJETIVO: Investigar la presencia de amiloidosis secundaria (AA) en pacientes con diagnóstico de artritis reumatoide (AR). MATERIALES Y MÉTODOS: Se evaluó tiempo de enfermedad (TE), presencia de manifestaciones extraarticulares, capacidad funcional y estadio de progresión anatómica, hemograma, velocidad de sedimentación globular, factor reumatoide (FR) (Test de Látex), albúmina sérica y examen completo de orina. Se realizó aspirado de grasa subcutánea periumbilical. El tejido se coloreó con rojo Congo y observó por microscopía óptica y luz polarizada, siendo positiva la birrefringencia verde manzana. RESULTADOS: Se estudió 81 pacientes con diagnóstico de AR (criterios del ACR), 71 fueron mujeres y 10 varones, con rango de edad 31 a 80 años. 75/81 fueron FR (+), 3/81 AA (+). El TE promedio fue 14,74 años para los AA (-) y 20,3 para los AA (+). Sólo en un paciente se halló amiloide en biopsia renal. CONCLUSIONES: En nuestra serie la frecuencia fue menor a lo reportado. Los pacientes con amiloidosis tuvieron títulos altos de FR y TE más prolongado

Biopsia de Grasa Subcutánea para el Diagnóstico de Amiloidosis Secundaria en Artritis Reumatoide

OBJECTIVE: To detect secondary amyloidosis (AA) in patients with rheumatoid arthritis (RA). MATERIAL AND METHODS: We assayed length of disease, extraarticular involvement, functional ability, anatomical compromise, white cell count, erythrocyte sedimentation rate, rheumatoid factor (RF) (latex test), serum albumin, and urine analysis. All of patients underwent periumbilical aspirate of subcutaneous fat. Samples were stained with Congo red, and light microscopy and polarized microscopy were used. Green-apple birefrigence was taken as AA (+). RESULTS: We studied 81 patients with RA (ACR criteria), 71 of them were females. The ages were between 31 and 80 years. 75/81 patients were RF (+), 3/81 were AA (+). Average length of disease was 14,74 years in AA (-) patients and 20,3 years in AA (+). Just one patient showed renal deposits of amyloid. CONCLUSION: Our occurrence of amyloidosis in patients with AR was lower. Patients with secondary amiloidosis and AR had higher RF levels and larger length of disease.OBJETIVO: Investigar la presencia de amiloidosis secundaria (AA) en pacientes con diagnóstico de artritis reumatoide (AR). MATERIALES Y MÉTODOS: Se evaluó tiempo de enfermedad (TE), presencia de manifestaciones extraarticulares, capacidad funcional y estadio de progresión anatómica, hemograma, velocidad de sedimentación globular, factor reumatoide (FR) (Test de Látex), albúmina sérica y examen completo de orina. Se realizó aspirado de grasa subcutánea periumbilical. El tejido se coloreó con rojo Congo y observó por microscopía óptica y luz polarizada, siendo positiva la birrefringencia verde manzana. RESULTADOS: Se estudió 81 pacientes con diagnóstico de AR (criterios del ACR), 71 fueron mujeres y 10 varones, con rango de edad 31 a 80 años. 75/81 fueron FR (+), 3/81 AA (+). El TE promedio fue 14,74 años para los AA (-) y 20,3 para los AA (+). Sólo en un paciente se halló amiloide en biopsia renal. CONCLUSIONES: En nuestra serie la frecuencia fue menor a lo reportado. Los pacientes con amiloidosis tuvieron títulos altos de FR y TE más prolongado

Factores asociados a infecciones serias en pacientes hospitalizados con lupus eritematoso sistémico

Introduction. Lupus patients have an increased risk of developing infections due to the disease, use of immunosuppressants and corticosteroids. Objective. To identify the associated factors for serious infections in lupus patients in a national referral hospital. Retrospective, analytical, case-control study in the Rheumatology Service of the Guillermo Almenara Irigoyen National Hospital, Lima, Peru. Methods. The registry of hospitalized patients in the study period was analyzed, the cases were patients in whom the etiology of the first infection developed their hospitalization. Controls were hospitalized lupus patients without infections in the same study period. Variables predisposing to the development of infections were analyzed. Results. 61 patients out of 390 hospitalized developed infections during their hospitalization. 48 developed 1 only infectious event (in 40 an etiology developed). The cases had higher damage, activity and comorbidity compared to the controls. In the univariate analysis, salary (p = 0.031), use of immunosuppressants upon admission (previous: p = 0.004 and current: p = 0.004), use of glucocorticoids (&lt;30 days: p = 0.015 and&gt; 30-360 days: p = 0.028), activity (p = 0.029) and damage (p = 0.026) produced by the disease and length of hospitalization (p = 0.045), had a statistically significant association. In the multivariate analysis, the days of hospitalization were associated with the development of infections. Conclusions. There is an association between days of hospitalization and the development of serious infections in lupus patients in the study period.Introducción. En pacientes con lupus eritematoso sistémico (LES) existe incremento de infecciones debido a la propia enfermedad, al uso de inmunosupresores y corticoides. Objetivo. Identificar los factores asociados a infecciones serias en pacientes lúpicos en un hospital de referencia nacional. Estudio retrospectivo, analítico, de casos y controles en el Servicio de Reumatología del Hospital Nacional Guillermo Almenara Irigoyen, Lima, Perú. Métodos. Se analizó el registro de pacientes hospitalizados en el periodo de estudio, los casos fueron pacientes en los que se demostró la etiología de la primera infección durante su hospitalización. Los controles fueron pacientes lúpicos hospitalizados sin infecciones en el mismo periodo de estudio. Se analizaron variables asociadas al desarrollo de infecciones. Resultados. 61 pacientes de 390 hospitalizados desarrollaron infecciones durante su hospitalización. 48 desarrollaron 1 solo evento infeccioso (en 40 se demostró etiología). Los casos tuvieron mayor actividad, daño y comorbilidad en comparación con los controles. En el análisis univariado, el salario (p=0,031), el uso de inmunosupresores a la admisión (previo: p=0,004 y actual: p=0,004), el uso de glucocorticoides (&lt;30 días: p=0,015 y &gt;30-360 días: p=0,028), la actividad (p=0,029) y el daño (p=0,026) producido por la enfermedad, y el tiempo de hospitalización (p=0,045) tuvieron asociación estadísticamente significativa. En el análisis multivariado, los días de hospitalización se asociaron al desarrollo de infecciones. Conclusiones. Existió asociación entre días de hospitalización y el desarrollo de infecciones serias en pacientes lúpicos durante el periodo de estudio

Genome-Wide Association Study in an Amerindian Ancestry Population Reveals Novel Systemic Lupus Erythematosus Risk Loci and the Role of European Admixture

OBJECTIVES: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a strong genetic component. Our aim was to perform the first genome-wide association study on individuals from the Americas enriched for Native American heritage. MATERIALS AND METHODS: We analyzed 3,710 individuals from four countries of Latin America and the Unites States diagnosed with SLE and healthy controls. Samples were genotyped with the HumanOmni1 BeadChip. Data of out-of-study controls was obtained for the HumanOmni2.5. Statistical analyses were performed using SNPTEST and SNPGWA. Data was adjusted for genomic control and FDR. Imputation was done using IMPUTE2, and HiBAG for classical HLA alleles. RESULTS: The IRF5-TNPO3 region showed the strongest association and largest odds ratio (OR) (rs10488631, P(gcadj) = 2.61×10(−29), OR = 2.12, 95% CI: 1.88–2.39) followed by the HLA class II on the DQA2-DQB1 loci (rs9275572, P(gcadj) = 1.11 × 10(−16), OR = 1.62, 95% CI: 1.46–1.80; rs9271366, P(gcadj)=6.46 × 10(−12), OR = 2.06, 95% CI: 1.71–2.50). Other known SLE loci associated were ITGAM, STAT4, TNIP1, NCF2 and IRAK1. We identified a novel locus on 10q24.33 (rs4917385, P(gcadj) =1.4×10(−8)) with a eQTL effect (P(eqtl)=8.0 × 10(−37) at USMG5/miR1307), and describe novel loci. We corroborate SLE-risk loci previously identified in European and Asians. Local ancestry estimation showed that HLA allele risk contribution is of European ancestral origin. Imputation of HLA alleles suggested that autochthonous Native American haplotypes provide protection. CONCLUSIONS: Our results show the insight gained by studying admixed populations to delineate the genetic architecture that underlies autoimmune and complex diseases

Genome-Wide Association Study in an Amerindian Ancestry Population Reveals Novel Systemic Lupus Erythematosus Risk Loci and the Role of European Admixture

OBJECTIVES: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a strong genetic component. Our aim was to perform the first genome-wide association study on individuals from the Americas enriched for Native American heritage. MATERIALS AND METHODS: We analyzed 3,710 individuals from four countries of Latin America and the Unites States diagnosed with SLE and healthy controls. Samples were genotyped with the HumanOmni1 BeadChip. Data of out-of-study controls was obtained for the HumanOmni2.5. Statistical analyses were performed using SNPTEST and SNPGWA. Data was adjusted for genomic control and FDR. Imputation was done using IMPUTE2, and HiBAG for classical HLA alleles. RESULTS: The IRF5-TNPO3 region showed the strongest association and largest odds ratio (OR) (rs10488631, P(gcadj) = 2.61×10(−29), OR = 2.12, 95% CI: 1.88–2.39) followed by the HLA class II on the DQA2-DQB1 loci (rs9275572, P(gcadj) = 1.11 × 10(−16), OR = 1.62, 95% CI: 1.46–1.80; rs9271366, P(gcadj)=6.46 × 10(−12), OR = 2.06, 95% CI: 1.71–2.50). Other known SLE loci associated were ITGAM, STAT4, TNIP1, NCF2 and IRAK1. We identified a novel locus on 10q24.33 (rs4917385, P(gcadj) =1.4×10(−8)) with a eQTL effect (P(eqtl)=8.0 × 10(−37) at USMG5/miR1307), and describe novel loci. We corroborate SLE-risk loci previously identified in European and Asians. Local ancestry estimation showed that HLA allele risk contribution is of European ancestral origin. Imputation of HLA alleles suggested that autochthonous Native American haplotypes provide protection. CONCLUSIONS: Our results show the insight gained by studying admixed populations to delineate the genetic architecture that underlies autoimmune and complex diseases