Clinical and Descriptive Study of Orofacial Clefts in Colombia: 2069 Patients From Operation Smile Foundation.

OBJECTIVE: To describe the population of patients with cleft lip and/or palate (CL/P) in terms of cleft phenotypes, gender, age, ethnic group, family history, clinical presentation (syndromic vs nonsyndromic), some environmental and behavioral factors, and some clinical features. DESIGN: Descriptive retrospective study. SETTING: Patients attending the genetics counseling practice in Operation Smile Foundation, Bogotá, Colombia, for over 8 years. PARTICIPANTS: No screening was conducted. All patients requiring clinical genetics assessment in Operation Smile Foundation were included in the study. RESULTS: Left cleft lip and palate (CLP) and nonsyndromic forms were the most frequent types of malformations in this population. Psychomotor retardation and heart disease were the most frequent comorbidities in these patients. A low proportion of mothers exposed to passive smoking during pregnancy was observed and low birth weight accounted for an important number of cases. Aarskog, velocardiofacial, and orofaciodigital syndromes were the most frequent syndromic forms of CLP in this population. CONCLUSIONS: In this study, the most frequent type of CL/P was the nonsyndromic complete left CLP. Aarskog, velocardiofacial, and orofaciodigital syndromes were the most frequent syndromic forms of CL/P in this population.

Frequency of 14 genetic variants associated with breast cancer risk and treatment in a Colombian population / Frecuencia de 14 variantes genéticas asociadas con el riesgo y el tratamiento del cáncer de mama en una población colombiana

SUMMARY Introduction: Genetic variations have been related to risk and treatment efficacy. Many polymorphisms in breast cancer are known to influence susceptibility, breast cancer risk and treatment outcome. Polymorphisms vary among populations; therefore, local studies are necessary. Objective: To establish the frequency of polymorphisms associated to breast cancer risk and treatment pharmacogenomics in a group of Colombian individuals. Methods: Data from microarray profiles including gene polymorphisms associated with breast cancer treatment were retrospectively collected (Pathway Genomics®). The frequency of marker CYP2D6 rs3892097 and a breast cancer panel (CAS8 rs1045485, CHEK21100delC, ESR1 rs2046210, FGFR2 rs1219648, intergenic_2q35rs13387042, intergenic_8q24 rs13281615, MSRP30 rs10941679, TNRC9 rs3803662, AKAP9 rs6964587, LSP1 rs3817198, MAP3K1rs889312, PALBS1592 delT, ESR1 rs3020314) were studied. Results: Microarray data from 68 men and 92 women were analyzed. All polymorphisms were in Hardy-Weinberg equilibrium. Genotypic frequencies of CYP2D6 rs3892097 C/T, CAS8 rs1045485 G/C, and those of genes included in a breast cancer panel (CAS8 rs1045485, CHEK21100delC, FGFR2rs1219648, intergenic_2q35rs13387042, intergenic_8q24 rs13281615, MSRP30 rs10941679, TNRC9 rs3803662, LSP1 rs3817198, MAP3K1rs889312, PALBS1592 del T, ESR1rs3020314) did not significantly differ from previously published data. ESR1 rs2046210, with allele frequencies of C=0.04 and T=0.02, and AKAP9 rs6964587, with a frequency of A=0.005, were determined as rare. Conclusions: The population studied was not significantly different in allele distribution from previously reported data at HapMap. Genotypes in Colombian population are similar to other previously studied groups of healthy subjects. Extended use of genotyping pharmacogenetic polymorphisms will prevent toxicity and adverse effects in tamoxifen treatment (for example in CYP2D6 rs3892097). Therefore, therapeutic alternatives should be evaluated based on individual pharmacogenetic studies.

RESUMEN Introducción: las variaciones genéticas se han relacionado con el riesgo y la eicacia del tratamiento. Es sabido que muchos polimorfismos en cáncer de mama influyen en la susceptibilidad, el riesgo de cáncer y el resultado del tratamiento. Los polimorfismos varían entre las poblaciones, y por tanto, es necesario realizar estudios locales. Objetivo: establecer la frecuencia de polimorismos asociados al riesgo de cáncer de mama y la farmacogenómica del tratamiento en un grupo de individuos colombianos. Métodos: los datos de los perfiles de microarreglos, incluidos los polimorismos genéticos asociados con el tratamiento del cáncer de mama, se obtuvieron de forma retrospectiva (Pathway Genomics®). Se estudiaron la frecuencia del marcador CYP2D6 rs3892097 y un panel de cáncer de mama (CAS8 rs1045485, CHEK21100delC, ESR1 rs2046210,FGFR2 rs1219648, intergenic_2q35rs13387042, intergenic_8q24 rs13281615, MSRP30 rs10941679, TNRC9 rs3803662, AKAP9 rs6964587, LSP1 rs3817198, MAP3K1rs889312, PALBS1592 delT, ESR1 rs3020314). Resultados: se analizaron los datos de microarreglos de 68 hombres y 92 mujeres. Todos los polimorfismos siguieron el equilibrio Hardy-Weinberg. Las frecuencias fenotípicas de CYP2D6 rs3892097 C/T, CAS8 rs1045485 G/C, y aquellas de los genes incluidos en un panel de cáncer de mama (CAS8 rs1045485, CHEK21100delC, FGFR2rs1219648, intergenic_2q35rs13387042, intergenic_8q24 rs13281615, MSRP30 rs10941679, TNRC9 rs3803662, LSP1 rs3817198, MAP3K1rs889312, PALBS1592 del T, ESR1rs3020314) no difirieron significativamente de los datos publicados previamente. ESR1 rs2046210, con frecuencias alélicas de C = 0,04 y T = 0,02, y AKAP9 rs6964587, con una frecuencia de A = 0,005, se determinaron como raras.

Medicina genómica en Cardiología / Genomic Medicine in Cardiology

El desarrollo de nuevas tecnologías y el conocimiento de la secuencia del genoma humano, han abierto la posibilidad de estudiarlo a precios asequibles para los pacientes y las instituciones de salud, permitiendo su aplicación en enfermedades de alta prioridad como las cardiovasculares, la diabetes y el cáncer. En los últimos años, la secuencia del genoma a gran escala ha llevado a descubrimientos de variantes de genes que confieren riesgo a muchas enfermedades comunes y complejas. En medicina cardiovascular se han hecho una serie de descubrimientos de variantes de secuencias que están asociadas a trastornos como la enfermedad de las arterias coronarias, la fibrilación auricular, la enfermedad vascular periférica, el aneurisma de la aorta y el ictus isquémico. Por tanto, una buena proporción de datos genéticos se ha acumulado en cardiología y estos han aumentado la comprensión de una serie importante de enfermedades. Mediante el estudio de las variantes genéticas polimórficas asociadas a los riesgos para diferentes enfermedades, surge un potencial en la medicina predictiva y preventiva. En la actualidad, los laboratorios clínicos ofrecen estudios de más de 30.000 variantes asociadas con la susceptibilidad genética, a las que médicos y pacientes pueden acceder cada vez con mayor facilidad. Estos exámenes permiten establecer un plan preventivo personalizado en salud. Mientras que hoy los criterios de manejo terapéutico son fenotípicos (edad, índice de masa corporal, cuadro hemático o función renal, por ejemplo), se están descuidando las particularidades genéticas individuales de los pacientes y de sus enfermedades. De ahí que es fundamental considerar los polimorfismos genéticos relevantes para mejorar la caracterización de enfermedades cardiovasculares prevalentes e incidentes, tanto para seleccionar la terapia apropiada, como para definir los medicamentos y las dosis adecuadas para cada paciente.

Using vaginal wall impedance to determine estrous cycle phase in Lewis rats.

The use of Lewis rats in embryonic tissue transplantation experiments can present a challenge because of the fertility problems associated with this strain. The authors used estrous cycle phase determination to time pairings of reproductively active females and males in order to increase the likelihood that mating would occur. During a 24-month period, female rats in a production colony were evaluated for estrous phase by microscopic evaluation of vaginal smears and by vaginal impedance readings. Pairings that were arranged with females determined to be in the proestrous phase by vaginal smears resulted in a low rate of confirmed matings (14%). Serial vaginal smear sampling also produced a high incidence of pseudopregnancy. Pairings that were arranged with females determined to be in the proestrous phase by vaginal impedance readings resulted in a high rate of confirmed matings (48.1%) as well as a high rate of pregnancy (29.4%). An average of 7.2 embryos were produced per pregnancy. The vaginal impedance technique can be used to improve the breeding success rate of Lewis rats in order to maintain a stable production of embryos for experimentation.