Particularidades genéticas y bioquímicas de la hipercolesterolemia familiar en el suroeste de la Península Ibérica / Genetics and biochemistry of familial hypercholesterolemia in Southwest of the Iberian Peninsula

Hasta el momento, la mayor parte de los casos de hipercolesterolemia familiar (60-80%) se atribuyen a variantes patogénicas en el gen LDLR. Solo un 1-5% de los casos se produce por variantes en el gen APOB y un 0-3% por variantes en el gen PCSK9. Existen gran variedad en mutaciones patogénicas conocidas del gen LDLR mientras que, para las que afectan al gen APOB, la de mayor incidencia es p.Arg3527Gln, descrita predominantemente en poblaciones de Centroeuropa y América del Norte. En la Península Ibérica el gen predominante afectado es el del receptor de LDL, similar al resto del mundo, siendo la afectación del gen APOB descrita en individuos del noroeste y anecdótica en el resto del territorio. Analizamos genéticamente la población asistida en el primer año de una consulta de lípidos del suroeste de España con puntuación≥6 puntos de las clínicas de lípidos holandesas y describimos los hallazgos genéticos, bioquímicos y clínicos. Los primeros hallazgos muestran indicios de una posible mayor prevalencia de pacientes con mutación en el gen APOB respecto a otros territorios. Encontramos hechos históricos que darían una posible explicación a este hecho, apoyando así dicha presunción.(AU)

So far, most cases of hypercholesterolaemia (60-80%) are attributed to pathogenic variants in the LDLR gene. Only 1-5% of cases are caused by variants in the APOB gene, and 0-3% by variants in the PCSK9 gene. There is a large variety in known pathogenic mutations of the LDLR gene, while for those affecting the APOB gene, the highest incidence is p.Arg3527Gln, described predominantly in Central European and North American populations. In the Iberian Peninsula the predominant gene affected is that of the LDL receptor, similar to the rest of the world, with the involvement of the APOB gene being described in individuals from the northwest, and anecdotal in the rest of the territory. A genetics analysis was performed on the population attending the first year of a lipid clinic in southwestern Spain with a 6-point score from the Dutch lipid clinics. The genetic, biochemical and clinical findings are described. The first findings show indications of a possible higher prevalence of patients with mutation in the APOB gene compared to other territories. Historical evidence is presented that could give a possible explanation to this, thus supporting the assumption.(AU)

Genetics and biochemistry of familial hypercholesterolemia in Southwest of the Iberian Peninsula. / Particularidades genéticas y bioquímicas de la hipercolesterolemia familiar en el suroeste de la Península Ibérica.

So far, most cases of hypercholesterolaemia (60-80%) are attributed to pathogenic variants in the LDLR gene. Only 1-5% of cases are caused by variants in the APOB gene, and 0-3% by variants in the PCSK9 gene. There is a large variety in known pathogenic mutations of the LDLR gene, while for those affecting the APOB gene, the highest incidence is p.Arg3527Gln, described predominantly in Central European and North American populations. In the Iberian Peninsula the predominant gene affected is that of the LDL receptor, similar to the rest of the world, with the involvement of the APOB gene being described in individuals from the northwest, and anecdotal in the rest of the territory. A genetics analysis was performed on the population attending the first year of a lipid clinic in southwestern Spain with a 6-point score from the Dutch lipid clinics. The genetic, biochemical and clinical findings are described. The first findings show indications of a possible higher prevalence of patients with mutation in the APOB gene compared to other territories. Historical evidence is presented that could give a possible explanation to this, thus supporting the assumption.