Daño oxidativo y capacidad de defensa antioxidante en pacientes cubanos con mucopolisacaridosis / Oxidative damage and anti-oxidant defense capacity in Cuban patients with mucopolysaccharidosis

Introducción: Las mucopolisacaridosis son causadas por la deficiencia de las actividades de las enzimas lisosomales necesarias para degradar los glicosaminoglicanos. Estos síndromes comparten muchas características clínicas aunque en grados variables. Las manifestaciones clínicas implican múltiples sistemas de órganos y algunas tienen terapia de reemplazo enzimático. En muchas investigaciones se hace alusión a la presencia de estrés oxidativo en quienes la padecen, pero esta condición aún no se ha estudiado en los pacientes cubanos. Objetivo: Evaluar parámetros de estrés oxidativo en pacientes cubanos con mucopolisacaridosis. Métodos: Se realizó un estudio de casos y controles que incluyó a 7 niños con mucopolisacaridosis de tipos I, II, III y IV (casos) y a 21 aparentemente sanos, pareados en edad y sexo (controles). Se midieron los niveles plasmáticos de malonildialdehído, productos avanzados de oxidación de proteínas, grupos tiol libres y marcadores de química sanguínea. Se cuantificaron las actividades intraeritrocíticas de superóxido dismutasa, catalasa y de glutatión peroxidasa. Todas las técnicas utilizadas fueron espectrofotométricas. Resultados: Los pacientes mostraron un aumento tanto en los niveles de calcio como en la oxidación de lípidos y proteínas, en comparación con los controles y los valores de referencia de Cuba. Hubo una disminución en la actividad de la enzima superóxido dismutasa y las concentraciones de grupos tioles. No se encontraron diferencias para el resto de los parámetros medidos. Conclusiones: El aumento del daño oxidativo y la disminución de la capacidad antioxidante sugieren la presencia de estrés oxidativo en esos pacientes cubanos.

Introduction: Mucopolysaccharidosis are caused by the deficiency in lysosomal enzyme activities necessary to degrade the glycosaminoglycans. These syndromes share many clinical characteristics although in variable degrees. Clinical manifestations imply multiple organs systems and some have enzyme replacement treatment. Many investigations deal on the presence of oxidative stress in those who suffer it, but this condition has not still been studied in Cuban patients. Objective: To evaluate parameters of oxidative stress in Cuban patients with mucopolysaccharidosis. Methods: A cases and controls study which included 7 children with mucopolysaccharidosis types I, II, III and IV (cases) and 21 apparently healthy children, paired by age and sex (control group) was carried out. The plasmatic levels of malondialdehide, advanced products of proteins oxidation, free thiol groups and blood chemistry markers were measured. The intraerythrocytic activities of superoxide dismutase, catalase and that of glutathione peroxidase were quantified. All the used techniques were spectrophotometrical. Results: The patients showed an increase, both in the calcium levels as in the oxidation of proteins and lipids, in comparison with the control group and the Cuban values reference. There was a decrease in the activity of the enzyme superoxide dismutase and the concentrations of thiols groups. There were no differences for the rest of the measured parameters. Conclusions: The increase of the oxidative damage and the decrease of the anti-oxidant capacity suggest the presence of oxidative stress in those Cuban patients.

Meta-analysis of GWA studies provides new insights on the genetic architecture of skin pigmentation in recently admixed populations.

BACKGROUND: Association studies in recently admixed populations are extremely useful to identify the genetic architecture of pigmentation, due to their high genotypic and phenotypic variation. However, to date only four Genome-Wide Association Studies (GWAS) have been carried out in these populations. RESULTS: We present a GWAS of skin pigmentation in an admixed sample from Cuba (N = 762). Additionally, we conducted a meta-analysis including the Cuban sample, and admixed samples from Cape Verde, Puerto Rico and African-Americans from San Francisco. This meta-analysis is one of the largest efforts so far to characterize the genetic basis of skin pigmentation in admixed populations (N = 2,104). We identified five genome-wide significant regions in the meta-analysis, and explored if the markers observed in these regions are associated with the expression of relevant pigmentary genes in human melanocyte cultures. In three of the regions identified in the meta-analysis (SLC24A5, SLC45A2, and GRM5/TYR), the association seems to be driven by non-synonymous variants (rs1426654, rs16891982, and rs1042602, respectively). The rs16891982 polymorphism is strongly associated with the expression of the SLC45A2 gene. In the GRM5/TYR region, in addition to the rs1042602 non-synonymous SNP located on the TYR gene, variants located in the nearby GRM5 gene have an independent effect on pigmentation, possibly through regulation of gene expression of the TYR gene. We also replicated an association recently described near the MFSD12 gene on chromosome 19 (lead variant rs112332856). Additionally, our analyses support the presence of multiple signals in the OCA2/HERC2/APBA2 region on chromosome 15. A clear causal candidate is the HERC2 intronic variant rs12913832, which has a profound influence on OCA2 expression. This variant has pleiotropic effects on eye, hair, and skin pigmentation. However, conditional and haplotype-based analyses indicate the presence of other variants with independent effects on melanin levels in OCA2 and APBA2. Finally, a follow-up of genome-wide signals identified in a recent GWAS for tanning response indicates that there is a substantial overlap in the genetic factors influencing skin pigmentation and tanning response. CONCLUSIONS: Our meta-analysis of skin pigmentation GWAS in recently admixed populations provides new insights about the genetic architecture of this complex trait.

Exploring Cuba's population structure and demographic history using genome-wide data.

Cuba is the most populated country in the Caribbean and has a rich and heterogeneous genetic heritage. Here, we take advantage of dense genomic data from 860 Cuban individuals to reconstruct the genetic structure and ancestral origins of this population. We found distinct admixture patterns between and within the Cuban provinces. Eastern provinces have higher African and Native American ancestry contributions (average 26% and 10%, respectively) than the rest of the Cuban provinces (average 17% and 5%, respectively). Furthermore, in the Eastern Cuban region, we identified more intense sex-specific admixture patterns, strongly biased towards European male and African/Native American female ancestries. Our subcontinental ancestry analyses in Cuba highlight the Iberian population as the best proxy European source population, South American and Mesoamerican populations as the closest Native American ancestral component, and populations from West Central and Central Africa as the best proxy sources of the African ancestral component. Finally, we found complex admixture processes involving two migration pulses from both Native American and African sources. Most of the inferred Native American admixture events happened early during the Cuban colonial period, whereas the African admixture took place during the slave trade and more recently as a probable result of large-scale migrations from Haiti.

Respuesta autoinmune en pacientes con enfermedades genéticas y desregulación del sistema inmune / Autoimmune response in patients with genetic diseases and immune system deregulation

Introducción: se han identificado diversas enfermedades genéticas donde se describen trastornos inmunológicos. Por otra parte las enfermedades autoinmunes son de origen multifactorial y se ha demostrado que factores genéticos como el complejo principal de histocompatibilidad predisponen a la autoinmunidad. Objetivo: describir alteraciones de la respuesta autoinmune en pacientes con defectos genéticos y desregulación del sistema inmune. Materiales y Métodos: se realizó un estudio descriptivo. La muestra estuvo constituida por 20 pacientes con enfermedades genéticas y desregulación del Sistema inmune procedentes de la consulta de Genética Médica del Hospital Juan Manuel Márquez, con una distribución por sexo de 11 pacientes femeninos (55%) y 9 masculinos (45%). El rango de edades fue de 6 meses a 21 años para un promedio de 6,9 años. Los parámetros de autoinmunidad evaluados fueron: Factor reumatoideo y Anticuerpos contra el ADN de doble cadena, determinados mediante ensayos inmunoenzimáticos. Inmunocomplejos circulantes determinados por el método de precipitación y Anticuerpos antinucleares determinados por inmunofluorescencia indirecta. Resultados y Discusión: en la evaluación de la respuesta autoinmune la mayor positividad se obtuvo en la determinación de Inmunocomplejos circulantes (40 %) y Factor reumatoideo (40 %), lo cual puede corresponder a una hiperrespuesta del sistema inmune como consecuencia de las infecciones recurrentes que presentaron los pacientes. El 4% de los pacientes presentó Anticuerpos antinucleares. Los Anticuerpos contra el ADN, obtenidos en 35% de los pacientes, pueden producirse en condiciones clínicas diferentes y como respuesta inmunológica no patológicas. Conclusiones: en la investigación se evidenció que en pacientes con enfermedades genéticas y desregulación del sistema inmune es frecuente encontrar parámetros autoinmunes alterados.

Introduction: several genetic diseases with immunological disorder have been described. On the other hand autoimmune diseases have multi factorial origin and autoimmunity predisposition by genetic factors like histocompatibility principal complex has been demonstrated. Objective: describe autoimmune response disorder in patients with genetic defects and immune system deregulation. Material and Method: a descriptive study was carried out. Sample was constituted by 20 pacients with genetic defects and immune system deregulation, coming from Medical Genetic consult of Juan Manuel Márquez hospital, with sex distribution of 11 feminine (55%) and 9 masculine (45%) patients. Age interval was of 6 month and 21 years, for average of 6.9 years. Autoimmunity parameter studied were Rheumatoid factor and Anti double DNA chain antibodies determined by enzymatic immunoassay. Circulate immunecomplex determined by precipitation method and Antinuclear antibodies determined by indirect immunofluorescence. Results and Discussion: in evaluation of autoimmune response mayor positivity obtained was Circulate immunecomplex (40 %) and Rheumatoid factor (40 %) determinations, which may be correspond to an immune system hyper respond by recurrent infections consequence in patients. Antinuclear antibodies were present in 4% of patients. Anti double DNA chain antibodies, obtained in 35% of patients, can be produced in different clinical conditions and bay no pathological immune respond. Conclusions: investigation makes evident that patients with genetic defects and immune system deregulation have high frequency of alter autoimmune parameter.

Respuesta autoinmune en pacientes con enfermedades genéticas y desregulación del sistema inmune / Autoimmune response in patients with genetic diseases and immune system deregulation

Introducción: se han identificado diversas enfermedades genéticas donde se describen trastornos inmunológicos. Por otra parte las enfermedades autoinmunes son de origen multifactorial y se ha demostrado que factores genéticos como el complejo principal de histocompatibilidad predisponen a la autoinmunidad. Objetivo: describir alteraciones de la respuesta autoinmune en pacientes con defectos genéticos y desregulación del sistema inmune.Materiales y Métodos: se realizó un estudio descriptivo. La muestra estuvo constituida por 20 pacientes con enfermedades genéticas y desregulación del Sistema inmune procedentes de la consulta de Genética Médica del Hospital Juan Manuel Márquez, con una distribución por sexo de 11 pacientes femeninos (55 por ciento) y 9 masculinos (45 por ciento). El rango de edades fue de 6 meses a 21 años para un promedio de 6,9 años. Los parámetros de autoinmunidad evaluados fueron: Factor reumatoideo y Anticuerpos contra el ADN de doble cadena, determinados mediante ensayos inmunoenzimáticos. Inmunocomplejos circulantes determinados por el método de precipitación y Anticuerpos antinucleares determinados por inmunofluorescencia indirecta. Resultados y Discusión: en la evaluación de la respuesta autoinmune la mayor positividad se obtuvo en la determinación de Inmunocomplejos circulantes (40 por ciento) y Factor reumatoideo (40 por ciento), lo cual puede corresponder a una hiperrespuesta del sistema inmune como consecuencia de las infecciones recurrentes que presentaron los pacientes. El 4 por ciento de los pacientes presentó Anticuerpos antinucleares. Los Anticuerpos contra el ADN, obtenidos en 35 por ciento de los pacientes, pueden producirse en condiciones clínicas diferentes y como respuesta inmunológica no patológicas.Conclusiones: en la investigación se evidenció que en pacientes con enfermedades genéticas y desregulación del sistema inmune es frecuente encontrar parámetros autoinmunes alterados(AU)

Introduction: several genetic diseases with immunological disorder have been described. On the other hand autoimmune diseases have multi factorial origin and autoimmunity predisposition by genetic factors like histocompatibility principal complex has been demonstrated. Objective: describe autoimmune response disorder in patients with genetic defects and immune system deregulation. Material and Method: a descriptive study was carried out. Sample was constituted by 20 pacients with genetic defects and immune system deregulation, coming from Medical Genetic consult of Juan Manuel Márquez hospital, with sex distribution of 11 feminine (55 percent) and 9 masculine (45 percent) patients. Age interval was of 6 month and 21 years, for average of 6.9 years. Autoimmunity parameter studied were Rheumatoid factor and Anti double DNA chain antibodies determined by enzymatic immunoassay. Circulate immunecomplex determined by precipitation method and Antinuclear antibodies determined by indirect immunofluorescence. Results and Discussion: in evaluation of autoimmune response mayor positivity obtained was Circulate immunecomplex (40 percent) and Rheumatoid factor (40 percent) determinations, which may be correspond to an immune system hyper respond by recurrent infections consequence in patients. Antinuclear antibodies were present in 4 percent of patients. Anti double DNA chain antibodies, obtained in 35 percent of patients, can be produced in different clinical conditions and bay no pathological immune respond. Conclusions: investigation makes evident that patients with genetic defects and immune system deregulation have high frequency of alter autoimmune parameter(AU)