Abstract
It has been proposed that functional mutations in the melanocortin 4 receptor (MC4R) gene have an important impact in body mass index, being considered as a major susceptibility gene for obesity. A number of mutations have been reported in the MC4R gene in subjects from different countries and ethnic groups. However, no reports of MC4R mutations are have been published for South American populations. In this study, DNA samples of thirty-two unrelated obese women of Chilean origin were examined to search for genetic variants in the single exon of the gene through the use of single strand conformational polymorphism techniques and direct sequencing, leading to the identification of a Thr150Ile mutation in heterozygous status. The evaluation of family relatives of the index case for this mutation using PCR-RFLP analysis, identified two additional carriers in a three-generation family. Obesity, eating behavior and body composition phenotypes in this family revealed a possible relation of this variant with obesity in the presence of reduced penetrance. According to our knowledge, this is the first report of MC4R mutations in South American populations.
Resumen
Las mutaciones funcionales del receptor 4 de melanocortina (MC4R) tienen un impacto muy relevante sobre el índice de masa corporal, siendo considerado MC4R como un gen may or de susceptibilidad frente a la obesidad. Se han descrito mutaciones en este gen en diferentes grupos étnicos, aunque aún no existen publicaciones sobre variantes de MC4R en poblaciones de Sudamérica. En este estudio, se analizaron 32 mujeres obesas de Chile en la búsqueda de variantes genéticas en MC4R mediante uso de la técnica de polimorfismo conformacional de hebra simple, seguida de secuenciación bidireccional, encontrándose una portadora de la mutación Thr150Ile en heterocigosis. Se buscaron los familiares de este caso índice a través de tres generaciones, lo que llevó a la identificación de otras dos personas portadoras de esta mutación mediante técnicas de PCR-RFLP. La evaluación de fenotipos de obesidad, composición corporal y conducta alimentaria reveló la posible existencia de asociación de esta mutación con obesidad en presencia de penetrancia reducida. Hasta donde sabemos, este estudio representa la primera publicación sobre mutaciones en MC4R en poblaciones de Sudamérica.
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Santos, J.L., Amador, P., Valladares, M. et al. Obesity and eating behaviour in a three-generation chilean family with carriers of the Thr150Ile mutation in the melanocortin-4 receptor gene. J. Physiol. Biochem. 64, 205–210 (2008). https://doi.org/10.1007/BF03178843
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DOI: https://doi.org/10.1007/BF03178843