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.

Familial hypercholesterolemia: Molecular characterization of possible cases from the Azores Islands (Portugal).

Familial hypercholesterolemia (FH) is an autosomal dominant disorder of the cholesterol metabolism, which constitutes a risk factor for coronary arterial disease (CAD). In the Azores Islands (Portugal), where mortality from CAD doubles its rate comparatively to the rest of the country and where a high frequency of dyslipidemia has been reported, the prevalence and distribution of FH remain unknown. The molecular characterization of a group of 33 possible cases of FH of Azorean background was undertaken in this study. A DNA array was initially used to search mutations in the LDLR, APOB and PCSK9 loci in 10 unrelated possible cases of FH. No mutations were detected in the array; after sequencing the full LDLR gene, 18 variants were identified, corresponding to two missense (c.806G > A; c.1171G > A) and sixteen synonymous alterations. Six of the synonymous variants which are consistently described in the literature as associated with altered cholesterol levels were used to build haplotypes. The most frequent haplotype corresponded to TTCGCC (45%), a "risk" haplotype, formed exclusively by alleles that were reported to increase cholesterol levels. Some of the variants detected in the full sequencing of the LDLR gene fell within the ligand-binding domain of this gene, defined by exons 2 to 6. To add information as to the role of such variants, these exons were sequenced in the remaining 23 possible FH cases. Two missense alterations (c.185C > T; c.806G > A) were found in this subset of possible FH cases. The missense alteration c.185C > T, identified in one individual, is novel for the Portuguese population. In silico analysis was not conclusive for this alteration, whose role will have to be further investigated. This study represents the first approach to the establishment of the mutational profile of FH in the Azores Islands.

Relación entre tipo y cantidad de carbohidratos dietarios con el perfil lipídico y ApoB100 en adultos / Relationship between the type and quantity of dietary carbohydrates, and the lipid profile and ApoB100 in adults / Relação entre o tipo e a quantidade de carboidratos na dieta e o perfil lipídico e ApoB100 em adultos

Objetivo. Establecer si existe relación entre el tipo y la cantidad de carbohidratos dietarios consumidos habitualmente con los niveles plasmáticos de lípidos, lipoproteínas y apolipoproteína B100 (ApoB100) Materiales y métodos. La muestra estuvo conformada por la base de datos de 144 de profesores de la Universidad Javeriana que previamente hicieron parte de otra investigación y de la cual se empleo la información sobre su alimentación, niveles plasmáticos de lípidos, lipoproteínas y ApoB100. Para determinar la relación entre las variables dependientes e independientes se realizó análisis de correlación simple y múltiple, en los casos de no correlación, se aplicó la prueba Chi² de independencia para relacionar el consumo de carbohidratos totales, azúcares y fibra total. Adicionalmente el análisis de varianza de un factor comparó los niveles de lípidos, lipoproteínas y ApoB100 con el consumo de carbohidratos totales, azúcares y fibra. Resultados. 76 hombres y 68 mujeres. La mayor parte de la población consume por encima de la recomendación diaria de carbohidratos totales, los hombres presentaron mayor consumo de carbohidratos tipo azúcares y más elevados los niveles plasmáticos de triglicéridos y lipoproteínas de muy baja densidad (VLDL), mientras que mujeres presentaron niveles más elevados en sus lipoproteínas de alta densidad (HDL). Al relacionar gramos de cada tipo de carbohidratos, con los niveles de lípidos, lipoproteínas y ApoB100 no se encontró correlación significativa para ninguno de los casos (p>0,05). Conclusión. No se encontró relación significativa entre el tipo y la cantidad de carbohidratos consumidos con los niveles plasmáticos de lípidos, lipoproteínas y ApoB100.

Objective. To establish if there is any relationship between the type and amount of dietary carbohydrates commonly consumed and the plasmatic levels of lipids, lipoproteins and apolipoprotein B100 (ApoB100). Materials and methods. The final sample was conformed by the database of 144 lecturers of the Pontificia Universidad Javeriana who had previously participated in another survey and from which we used information on their food habits, plasmatic lipid levels, lipoproteins and ApoB100. To determine the relationship between the dependent and independent variables, simple and multiple correlation analyses were done. In the cases of no correlation we applied the independence Chi² test to find the relationship with the consumption of total carbohydrates, sugars and total fiber. Additionally, with a one-factor analysis of variance we compared plasmatic levels of lipids, lipoproteins and ApoB100 with the consumption of total carbohydrates, sugars and fiber. Results. Most of the population consumes above the daily total carbohydrate recommendation, men presented greater carbohydrate consumption of the type of sugars and more elevated plasmatic levels of triglycerides and lipoproteins of investivery low density (VLDL), whereas women presented higher levels of their high density lipoproteins (HDL). When relating grams of each type of carbohydrates with the levels of lipids, lipoproteins and ApoB100, no significant correlation was found for any of the cases (p>0,05). Conclusion. There was no significant relationship between the type and amount of carbohydrates consumed with the plasmatic levels of lipids, lipoproteins and Apo B100.

Objetivo. Estabelecer a possível relação entre o tipo e a quantidade de carboidratos na dieta normalmente consumida com os níveis plasmáticos de lipídios, lipoproteínas e apolipoproteína B100 (ApoB100). Materiais e métodos. A amostra consistiu de um banco de dados de 144 professores da "Universidad Javeriana" que anteriormente fizeram parte de outra pesquisa, e da qual foi utilizada a informação sobre sua alimentação, os níveis plasmáticos de lipídios, lipoproteínas e ApoB100. Para determinar a relação entre as variáveis dependentes e independentes foi realizada uma análise de correlação simples e múltipla, em casos de ausência de correlação foi usado o teste do Chi² de independência para relacionar o consumo dos carboidratos totais, açúcares e fibra total. Além disso, a análise de variância de um fator comparou os níveis de lipídios, lipoproteínas e ApoB100 com o consumo de carboidratos totais, açúcares e fibras. Resultados. 76 homens e 68 mulheres. A maior parte da população consome acima da dose diária recomendada de carboidratos totais, os homens apresentaram maior consumo de carboidratos tipo açúcares, e mais elevados os níveis plasmáticos de triglicérides e lipoproteínas de muito baixa densidade (VLDL), enquanto que as mulheres apresentaram níveis mais elevados em lipoproteína de alta densidade (HDL). Ao relacionar gramas de cada tipo de carboidratos com os níveis de lipídios, lipoproteínas e ApoB100, nenhuma correlação significativa foi encontrada para qualquer um dos casos (p> 0,05). Conclusão. Nenhuma relação significativa foi encontrada entre o tipo e a quantidade de carboidratos consumida com os níveis plasmáticos de lipídios, lipoproteínas e ApoB100.