Insuficiencia ovárica prematura / Premature ovarian failure

Introducción La menopausia es el paso final en el proceso denominado envejecimiento ovárico. La disminución relacionada con la edad en el número de folículos dicta el inicio de la irregularidad del ciclo y el cese final de la menstruación. En paralelo, la descomposición en la calidad de los ovocitos contribuye a la disminución gradual de la fertilidad y la aparición final de esterilidad.

Introduction Menopause is the final step in the process called ovarian aging. The decrease related to age in the number of follicles dictates the beginning of the irregularity of the cycle and the final cessation of menstruation. In parallel, the decomposition in the quality of the oocytes contributes to the gradual decrease of fertility and the final appearance of sterility.

Gene-gene interactions between DRD3, MRP4 and CYP2B6 polymorphisms and its influence on the pharmacokinetic parameters of efavirenz in HIV infected patients.

Genetic factors have a significant impact on the PK variability of EFV, much higher than other non-genetic factors, such as demography. In this work we have performed a comprehensive PG analysis of genes encoding the major metabolizing enzymes and transporters of EFV, establishing a clear relationship between the PK parameters and genetic factors, which explain 50% of the variability in EFV PK parameters. The most relevant associations for metabolizing enzymes were found in CYP2B6 (rs3745274), in agreement with previous studies. The influence of transporters on the kinetics of EFV was also proved with significant correlations between the PK parameters of EFV and MRP4 (rs1751034, rs2274407). Analysis of gene-gene interactions with CYP2B6 was particularly useful to reinforce the role of MRP4 and to reveal unknown associations, such as that of DRD3. However, the role of DRD3 cannot be a direct effect but an indirect one due to physical proximity of NAT and the DRD3 locus in the genome.

[Diagnosis and treatment with steroids for patients with Duchenne muscular dystrophy: experience and recommendations for Mexico. Administración del Patrimonio de la Beneficencia Pública. Asociación de Distrofia Muscular de Occidente]. / Diagnóstico y tratamiento con esteroides de pacientes con distrofia muscular de Duchenne: experiencia y recomendaciones para México.

Duchenne muscular dystrophy is a severe, debilitating and progressive disease that affects 1 in 3,500 live male births in the world. The diagnosis should be confirmed by genetic testing to identify the mutation in the DMD gene or muscle biopsy and immunostaining to demonstrate the absence of dystrophin. Although up to now continues to be an incurable disease, this does not mean it has no treatment. Treatment should be multidisciplinary, looking for the functionality of the patient and avoiding or correcting complications, mainly cardio-respiratory and skeletal. Many proposals have been evaluated and implemented with the aim of improving the quality of life for these patients. The long-term steroids have shown significant benefits, such as prolonging ambulation, reduce the need for spinal surgery, improve cardiorespiratory function and increase survival and the quality of life. This document presents the recommendations based on the experience of the working group and experts worldwide on the diagnosis and treatment with steroids for patients with Duchenne muscular dystrophy.

TITLE: Diagnostico y tratamiento con esteroides de pacientes con distrofia muscular de Duchenne: experiencia y recomendaciones para Mexico.La distrofia muscular de Duchenne es una enfermedad grave, incapacitante y progresiva que afecta a 1 de cada 3.500 recien nacidos varones alrededor del mundo. El diagnostico debera confirmarse mediante pruebas geneticas para identificar la mutacion en el gen DMD, o bien por biopsia muscular e inmunotincion para demostrar la ausencia de distrofina. Aunque actualmente continua siendo una enfermedad incurable, no significa que no tenga tratamiento. Este debe ser multidisciplinario, buscando la funcionalidad del paciente y evitando o corrigiendo las complicaciones, principalmente cardiorrespiratorias y esqueleticas. Se han evaluado e implementado multiples propuestas con la finalidad de mejorar la calidad de vida en estos pacientes. Los esteroides a largo plazo han demostrado importantes beneficios para los pacientes, prolongan la deambulacion, reducen la necesidad de cirugia de columna, mejoran la funcion cardiorrespiratoria, y aumentan la supervivencia y la calidad de vida. En este documento se presentan las recomendaciones con base en la experiencia del grupo de trabajo y de los expertos de ambito mundial sobre el diagnostico y el tratamiento con esteroides para los pacientes con distrofia muscular de Duchenne.

Diagnóstico y tratamiento con esteroides de pacientes con distrofia muscular de Duchenne: experiencia y recomendaciones para México / Diagnosis and treatment with steroids for patients with Duchenne muscular dystrophy: experience and recommendations for Mexico

La distrofia muscular de Duchenne es una enfermedad grave, incapacitante y progresiva que afecta a 1 de cada 3.500 recién nacidos varones alrededor del mundo. El diagnóstico deberá confirmarse mediante pruebas genéticas para identificar la mutación en el gen DMD, o bien por biopsia muscular e inmunotinción para demostrar la ausencia de distrofina. Aunque actualmente continúa siendo una enfermedad incurable, no significa que no tenga tratamiento. Éste debe ser multidisciplinario, buscando la funcionalidad del paciente y evitando o corrigiendo las complicaciones, principalmente cardiorrespiratorias y esqueléticas. Se han evaluado e implementado múltiples propuestas con la finalidad de mejorar la calidad de vida en estos pacientes. Los esteroides a largo plazo han demostrado importantes beneficios para los pacientes, prolongan la deambulación, reducen la necesidad de cirugía de columna, mejoran la función cardiorrespiratoria, y aumentan la supervivencia y la calidad de vida. En este documento se presentan las recomendaciones con base en la experiencia del grupo de trabajo y de los expertos de ámbito mundial sobre el diagnóstico y el tratamiento con esteroides para los pacientes con distrofia muscular de Duchenne (AU)

Duchenne muscular dystrophy is a severe, debilitating and progressive disease that affects 1 in 3,500 live male births in the world. The diagnosis should be confirmed by genetic testing to identify the mutation in the DMD gene or muscle biopsy and immunostaining to demonstrate the absence of dystrophin. Although up to now continues to be an incurable disease, this does not mean it has no treatment. Treatment should be multidisciplinary, looking for the functionality of the patient and avoiding or correcting complications, mainly cardio-respiratory and skeletal. Many proposals have been evaluated and implemented with the aim of improving the quality of life for these patients. The longterm steroids have shown significant benefits, such as prolonging ambulation, reduce the need for spinal surgery, improve cardiorespiratory function and increase survival and the quality of life. This document presents the recommendations based on the experience of the working group and experts worldwide on the diagnosis and treatment with steroids for patients with Duchenne muscular dystrophy (AU)

Impact of pharmacogenetics on CNS side effects related to efavirenz.

AIM: This article evaluates which genetic factors are involved in CNS toxicity related to long-term treatment with efavirenz (EFV) standard doses and their relationship with plasma concentrations. PATIENTS & METHODS: A total of 119 HIV-positive patients, in which 1350 EFV plasma concentrations, 68 SNPs and 14 EFV-related adverse effects (AEs) were analyzed. RESULTS: Overall, 32.77% of patients reported CNS toxicity and 8.40% had concentrations above the therapeutic range. A correlation was mainly found between patients with global CNS AEs and high EFV maximum steady-state plasma concentration (p = 1.47 × 10(-6)). A preliminary analysis confirmed that CYP2B6*6 (516G>T and 785A>G) was the most highly correlated (p = 0.005) with AEs and high plasma concentrations. In a second analysis adjusting for maximum steady-state plasma concentration, suggestive genetic associations were found between BCRP 421C>A, MRP1 816G>A, 5-HT2A 102C>T and different AEs. CONCLUSION: The finding of the involvement of these SNPs in EFV toxicity opens the door for further studies to confirm their validity and for their application in the future clinical practice. Original submitted 18 February 2013; Revision submitted 17 May 2013.

An overview of STRUCTURE: applications, parameter settings, and supporting software.

OBJECTIVES: We present an up-to-date review of STRUCTURE software: one of the most widely used population analysis tools that allows researchers to assess patterns of genetic structure in a set of samples. STRUCTURE can identify subsets of the whole sample by detecting allele frequency differences within the data and can assign individuals to those sub-populations based on analysis of likelihoods. The review covers STRUCTURE's most commonly used ancestry and frequency models, plus an overview of the main applications of the software in human genetics including case-control association studies (CCAS), population genetics, and forensic analysis. The review is accompanied by supplementary material providing a step-by-step guide to running STRUCTURE. METHODS: With reference to a worked example, we explore the effects of changing the principal analysis parameters on STRUCTURE results when analyzing a uniform set of human genetic data. Use of the supporting software: CLUMPP and distruct is detailed and we provide an overview and worked example of STRAT software, applicable to CCAS. CONCLUSION: The guide offers a simplified view of how STRUCTURE, CLUMPP, distruct, and STRAT can be applied to provide researchers with an informed choice of parameter settings and supporting software when analyzing their own genetic data.

Differentiation of African components of ancestry to stratify groups in a case-control study of a Brazilian urban population.

BACKGROUND: Balancing the subject composition of case and control groups to create homogenous ancestries between each group is essential for medical association studies. METHODS: We explored the applicability of single-tube 34-plex ancestry informative markers (AIM) single nucleotide polymorphisms (SNPs) to estimate the African Component of Ancestry (ACA) to design a future case-control association study of a Brazilian urban sample. RESULTS: One hundred eighty individuals (107 case group; 73 control group) self-described as white, brown-intermediate or black were selected. The proportions of the relative contribution of a variable number of ancestral population components were similar between case and control groups. Moreover, the case and control groups demonstrated similar distributions for ACA <0.25 and >0.50 categories. Notably a high number of outlier values (23 samples) were observed among individuals with ACA <0.25. These individuals presented a high probability of Native American and East Asian ancestral components; however, no individuals originally giving these self-described ancestries were observed in this study. CONCLUSIONS: The strategy proposed for the assessment of ancestry and adjustment of case and control groups for an association study is an important step for the proper construction of the study, particularly when subjects are taken from a complex urban population. This can be achieved using a straight forward multiplexed AIM-SNPs assay of highly discriminatory ancestry markers.

Differentiation of african components of ancestry to stratify groups in a Case–control study of a brazilian urban population

Background: Balancing the subject composition of case and control groups to create homogenous ancestries between each group is essential for medical association studies. Methods: We explored the applicability of single-tube 34-plex ancestry informative markers (AIM) single nucleotide polymorphisms (SNPs) to estimate the African Component of Ancestry (ACA) to design a future case-control association study of a Brazilian urban sample. Results: One hundred eighty individuals (107 case group; 73 control group) self-described as white, brown-intermediate or black were selected. The proportions of the relative contribution of a variable number of ancestral population components were similar between case and control groups. Moreover, the case and control groups demonstrated similar distributions for ACA 0.50 categories. Notably a high number of outlier values (23 samples) were observed among individuals with ACA <0.25. These individuals presented a high probability of Native American and East Asian ancestral components; however, no individuals originally giving these self-described ancestries were observed in this study. Conclusions: The strategy proposed for the assessment of ancestry and adjustment of case and control groups for an association study is an important step for the proper construction of the study, particularly when subjects are taken from a complex urban population. This can be achieved using a straight forward multiplexed AIM-SNPs assay of highly discriminatory ancestry markers.

Pharmacogenetics of OATP transporters reveals that SLCO1B1 c.388A>G variant is determinant of increased atorvastatin response.

AIMS: The relationship between variants in SLCO1B1 and SLCO2B1 genes and lipid-lowering response to atorvastatin was investigated. MATERIAL AND METHODS: One-hundred-thirty-six unrelated individuals with hypercholesterolemia were selected and treated with atorvastatin (10 mg/day/4 weeks). They were genotyped with a panel of ancestry informative markers for individual African component of ancestry (ACA) estimation by SNaPshot(®) and SLCO1B1 (c.388A>G, c.463C>A and c.521T>C) and SLCO2B1 (-71T>C) gene polymorphisms were identified by TaqMan(®) Real-time PCR. RESULTS: Subjects carrying SLCO1B1 c.388GG genotype exhibited significantly high low-density lipoprotein (LDL) cholesterol reduction relative to c.388AA+c.388AG carriers (41 vs. 37%, p = 0.034). Haplotype analysis revealed that homozygous of SLCO1B1*15 (c.521C and c.388G) variant had similar response to statin relative to heterozygous and non-carriers. A multivariate logistic regression analysis confirmed that c.388GG genotype was associated with higher LDL cholesterol reduction in the study population (OR: 3.2, CI95%:1.3-8.0, p < 0.05). CONCLUSION: SLCO1B1 c.388A>G polymorphism causes significant increase in atorvastatin response and may be an important marker for predicting efficacy of lipid-lowering therapy.

Pharmacogenetics of OATP Transporters Reveals That SLCO1B1 c.388A>G Variant Is Determinant of Increased Atorvastatin Response

Aims: The relationship between variants in SLCO1B1 and SLCO2B1 genes and lipid-lowering response to atorvastatin was investigated. Material and Methods: One-hundred-thirty-six unrelated individuals with hypercholesterolemia were selected andOPEN ACCESStreated with atorvastatin (10 mg/day/4 weeks). They were genotyped with a panel of ancestry informative markers for individual African component of ancestry (ACA) estimation by SNaPshot® and SLCO1B1 (c.388A>G, c.463C>A and c.521T>C) and SLCO2B1 (−71T>C) gene polymorphisms were identified by TaqMan® Real-time PCR. Results: Subjects carrying SLCO1B1 c.388GG genotype exhibited significantly high low-density lipoprotein (LDL) cholesterol reduction relative to c.388AA+c.388AG carriers (41 vs. 37%, p = 0.034). Haplotype analysis revealed that homozygous of SLCO1B1*15 (c.521C and c.388G) variant had similar response to statin relative to heterozygous and non-carriers. A multivariate logistic regression analysis confirmed that c.388GG genotype was associated with higher LDL cholesterol reduction in the study population (OR: 3.2, CI95%:1.3–8.0, p G polymorphism causes significant increase in atorvastatin response and may be an important marker for predicting efficacy of lipid-lowering therapy.

Insulinemia y resistencia a la insulina: factores de riesgo independiente para restenosis luego de angioplastia coronaria?

La angioplastia coronaria y trasluminal percutánea (ACTP) es un procedimiento aceptado para la revascularización miocárdica en pacientes seleccionados. Sin embargo, la restenosis coronaria (RC) se presenta entre 30-55 por ciento en los primeros seis meses luego del procedimiento. Han sido descritos muchos fenómenos en la fisiopatología de la RC y el resultado final es una proliferación y migración de células de músculo liso vascular (CMLV) con síntesis de matriz extracelular. La insulina y la hiperinsulinemia han sido consideradas por algunas observaciones como factores de riesgo en el desarrollo de l aterosclerosis por sus efectos como factor de crecimiento de CMLV. No conocemos la relación entre la insulina y el desarrollo de RC. Realizamos un estudio clínico prospectivo y correlacional en 27 pacientes sometidos a ACTP en forma exitosa, con factores de riesgo mayores controlados, a los cuales se les realizó un control angiográfico y una prueba de supresión de insulina con octreótido (somatostatina) para valorar la resistencia a la insulina en un período de 4-6 meses post-t ACTP. Seis mujeres y 21 hombres. Edad de 61+-2.83 años. Fracción de eyección de 0.59+-0.014. Se presentó RC (lesión >50 por ciento) en el 48.1 por ciento. No se evidenció diferencias significativas entre los pacientes con RC y sin RC en cuanto al índice de masa corporal, glicemias, colesterol total, triglicéridos, c-HDL, c-LDL, ácido úrico y lesión residual. Los niveles de insulina en ayunas (p=0.120), insulina pico (p=0.159), insulina a las 2 hrs postprandial (p=0.369) y elpromedio de glicemia en el clamp de insulina (GPFE) (p=0.922) tampoco evidenciaron diferencias estadísticas. Nuestros resultados en la población estudiada no mostraron correlación entre las cifras de insulina con el porcentaje de obstrucción coronaria post ACTP. Esperamos contar con una mayor población y otros estudios en esta área