RESUMO
La enfermedad de Hirschsprung (HSCR) está causada por la ausencia de células ganglionares en el intestino, debido a defectos en la migración de las células del sistema nervioso entérico durante el desarrollo embrionario. La incidencia es aproximadamente de uno en cada 5000 nacimientos, más frecuente en hombres que en mujeres. Hay dos fenotipos según la longitud del segmento aganglionar: corto (S-HSCR, 80% de los enfermos) y largo (L-HSCR, el 20%). Se han detectado variaciones en la secuencia codificante del proto-oncogén rEt en enfermos con HCSR, lo que sugiere predisposición genética a padecer la enfermedad. Nuestro trabajo ha consistido en encontrar y analizar polimorfismos (SNPs) asociados a la enfermedad, así como su distribución poblacional (sexo y tipo de segmento). En el estudio genético se han analizado dos polimorfismos presentes en el promotor del gen, así como un polimorfismo en el exón 13 fuertemente asociado con la enfermedad. Como poblaciones en este estudio se establecieron una de enfermos con HSCR esporádico y un grupo de individuos sanos.Los resultados obtenidos corroboran que la enfermedad es más frecuente en hombres que en mujeres. El genotipado de rEt indica que los alelos A y G del promotor (c.-200A>G y c.-196C>A) y G del exón 13 (c.2307T>G) están asociados a la población enferma. Los datos apuntan a que no existe relación entre el fenotipo de la enfermedad y la distribución de los polimorfismos analizados. Concluimos que la presencia de ciertos polimorfismos en la secuencia de rEt indica predisposición genética (combinada con otros factores genéticos o ambientales) a padecer la enfermedad (AU)
Hirschsprung disease (HSCR) is caused by the absence of ganglion cells in the intestine due to defects in the migration of enteric nervous system cells during embryologic development. The incidence is one in every 5000 births, more common in men than women. There are two main phenotypes according to the aganglionic segment length: Short (S-HSCR, (80% of patients) and Long (L-HSCR, 20%). Variations have been detected in the coding sequence of the rEt proto-oncogene in patients with HSCR, suggesting a genetic predisposition to the disease. Our aim is to find and analyze polymorphisms (SNPs) associated with the disease. We are interested also in stablish an association between sex and type of aganglionic segment. We analyzed the rEt promoter as well a polymorphism in exon 13 strongly associated to the disease. The populations for the study were a group of 56 patients with sporadic HSCR and 178 healthy controls.The results obtained show that the disease is more common in men than in women (3:1). The rEt genotype shows that alleles A and G of the promoter (c.-200A> G and c.-196C> A) and G of exon 13 (c.2307T> G) are associated with the affected population. Our data suggest neither association between the disease phenotype and the distribution of the polymorphisms analyzed nor with the sex of the patients. The presence of certain polymorphisms in the rEt sequence indicates a genetic predisposition (combined with other genetic or environmental factors) to the disease (AU)
Assuntos
Humanos , Doença de Hirschsprung/genética , Estudos de Associação Genética/métodos , Testes Genéticos/métodos , Predisposição Genética para Doença/genética , Análise de Sequência/métodos , Distribuição por SexoRESUMO
Hirschsprung disease (HSCR) is caused by the absence of ganglion cells in the intestine due to defects in the migration of enteric nervous system cells during embryologic development. The incidence is one in every 5000 births, more common in men than women. There are two main phenotypes according to the aganglionic segment length: Short (S-HSCR, (80% of patients) and Long (L-HSCR, 20%). Variations have been detected in the coding sequence of the RET proto-oncogene in patients with HSCR, suggesting a genetic predisposition to the disease. Our aim is to find and analyze polymorphisms (SNPs) associated with the disease. We are interested also in stablish an association between sex and type of aganglionic segment. We analyzed the RET promoter as well a polymorphism in exon 13 strongly associated to the disease. The populations for the study were a group of 56 patients with sporadic HSCR and 178 healthy controls. The results obtained show that the disease is more common in men than in women (3:1). The RET genotype shows that alleles A and G of the promoter (c.-200A > G and c.-196C > A) and G of exon 13 (c.2307T > G) are associated with the affected population. Our data suggest neither association between the disease phenotype and the distribution of the polymorphisms analyzed nor with the sex of the patients. The presence of certain polymorphisms in the RET sequence indicates a genetic predisposition (combined with other genetic or environmental factors) to the disease.
