A genetic variant in the LDLR promoter is responsible for part of the LDL-cholesterol variability in primary hypercholesterolemia

BACKGROUND: GWAS have consistently revealed that LDLR locus variability influences LDL-cholesterol in general population. Severe LDLR mutations are responsible for familial hypercholesterolemia (FH). However, most primary hypercholesterolemias are polygenic diseases. Although Cis-regulatory regions might be the cause of LDL-cholesterol variability; an extensive analysis of the LDLR distal promoter has not yet been performed. We hypothesized that genetic variants in this region are responsible for the LDLR association with LDL-cholesterol found in GWAS. METHODS: Four-hundred seventy-seven unrelated subjects with polygenic hypercholesterolemia (PH) and without causative FH-mutations and 525 normolipemic subjects were selected. A 3103 pb from LDLR (-625 to +2468) was sequenced in 125 subjects with PH. All subjects were genotyped for 4 SNPs (rs17242346, rs17242739, rs17248720 and rs17249120) predicted to be potentially involved in transcription regulation by in silico analysis. EMSA and luciferase assays were carried out for the rs17248720 variant. Multivariable linear regression analysis using LDL-cholesterol levels as the dependent variable were done in order to find out the variables that were independently associated with LDL-cholesterol. RESULTS: The sequencing of the 125 PH subjects did not show variants with minor allele frequency ≥ 10%. The T-allele from g.3131C > T (rs17248720) had frequencies of 9% (PH) and 16.4% (normolipemic), p < 0.00001. Studies of this variant with EMSA and luciferase assays showed a higher affinity for transcription factors and an increase of 2.5 times in LDLR transcriptional activity (T-allele vs C-allele). At multivariate analysis, this polymorphism with the lipoprotein(a) and age explained ≈ 10% of LDL-cholesterol variability. CONCLUSION: Our results suggest that the T-allele at the g.3131 T > C SNP is associated with LDL-cholesterol levels, and explains part of the LDL-cholesterol variability. As a plausible cause, the T-allele produces an increase in LDLR transcriptional activity and lower LDL-cholesterol levels

Stability of the feasible set in balanced transportation problems

In this paper we study the stability of the feasible set of a balanced transportation problem. A transportation problem is balanced when the total supply is equal to the total demand. One can easily see that when we make minor adjustments to the data (supply and demand), the resulting problem may lose the property of balance. Therefore, although the transportation problem is a particular case of linear programming, you cannot apply the familiar results of stability. For a fixed number of origins and destinations we have obtained a vector representation for any feasible solution of the transportation problem. We have used this representation to prove that the feasible set mapping is continuous. We have also proved that the extreme point set mapping is lower semi continuous.

Funcionamiento familiar y su relación con la satisfacción con la vida familiar en adolescentes con autismo

Families in which a member meets criteria for the diagnosis of Autism Spectrum Disorder (ASD) may present some vulnerability to construct dysfunctional family structures, becoming a risk factor that hinders the emotional development of their members. The present study aims to study the relationship between the type of family structure and the satisfaction with family life of 30 adolescents aged between 12 and 18 years. For this, the Family Functioning Scale FACES- 20 Spanish version has been used and the Satisfaction Scale with family life (ESVF). The results obtained in this sample, the type of family structure does not have a statistically significant relations hip with the satisfaction of family life. However, related and agglutinated families are those that relate positively, suggesting that, the greater family cohesion, the greater satisfaction with the family life of adolescents with ASD.Las familias en las que algún miembro cumple criterios para el diagnóstico de Trastorno del Espectro Autista (TEA, en adelante) pueden presentar cierta vulnerabilidad a construir estructuras familiares disfuncionales, constituyéndose en un factor de riesgo que dificulta el desarrollo emocional de sus miembros. El presente estudio tiene como objetivo el estudio de la relación entre el tipo de estructura familiar y la satisfacción con la vida familiar de 30 adolescentes con edades comprendidas entre los 12 y los 18 años. Para ello, se han utilizado la Escala de Funcionamiento familiar FACES- 20 versión española y la Escala de Satisfacción con la vida de familia (ESVF). Los resultados obtenidos en esta muestra, el tipo de estructura familiar no tiene una relación estadísticamente significativa con la satisfacción de la vida familiar. No obstante, las familias relacionadas y aglutinadas son las que se relacionan de forma positiva, sugiriendo que, a mayor cohesión familiar, mayor satisfacción con la vida de familia de los adolescentes con TEA

El perfeccionismo en adolescentes con trastornos de la conducta alimentaria

Perfectionism has been considered a significant risk factor for psychopathology and a typical personality characteristic in people suffering from eating disorders (ED). This study aims to know the relationship between perfectionism and depressive symptomatology, self-esteem and body dissatisfaction in adolescents diagnosed with ED. The sample was composed by 100 adolescents (M age = 14.91, SD = 1.094) diagnosed with ED who went outpatiently to a specific child-juvenile ED unit of the National Health System. All patients completed the perfectionism scale of the Inventory of Eating Disorders (EDI-3), the Spanish Child Depression Questionnaire (CEDI-II), the Rosenberg Self-Esteem Scale (RSES), and the Body Form Questionnaire (BSQ-34). Results indicate that the perfectionism scale of EDI-3 correlates significantly positively with CEDI-II (r =, 336, p =, 001) and BSQ-34 (r =, 199, p =, 45), and in a negative way with the RSES (r = -, 337, p =, 001). Adolescents diagnosed with ED who score higher on perfectionism show greater depressive symptoms and body dissatisfaction, and lower self-esteem. We believe that emphasizing the treatment of perfectionism could result in a psychopathological improvement of these patients.El perfeccionismo ha sido considerado un factor de riesgo significativo para la psicopatología y una característica de personalidad típica en las personas que sufren trastornos de la conducta alimentaria (TCA). Este estudio pretende conocer la relación entre el perfeccionismo y la sintomatología depresiva, autoestima e insatisfacción corporal en adolescentes diagnosticados de TCA. La muestra se compuso de 100 adolescentes (M edad = 14,91, DT = 1,094) diagnosticados de TCA que acudían ambulatoriamente a una unidad específica de TCA infanto-juvenil del Sistema Nacional de Salud. Todos los pacientes cumplimentaron la escala perfeccionismo del Inventario de Trastornos de la Conducta Alimentaria (EDI-3), el Cuestionario Español de Depresión Infantil (CEDI-II), la Escala de Autoestima de Rosenberg (RSES), y el Cuestionario sobre la Forma Corporal (BSQ-34). Los resultados indican que la escala perfeccionismo del EDI-3 correlaciona significativamente de forma positiva con el CEDI-II (r = ,336, p = ,001) y BSQ-34 (r = ,199, p = ,45), y de forma negativa con el RSES (r = -,337, p = ,001). Los adolescentes diagnosticados de TCA que puntúan más alto en perfeccionismo presentan mayor sintomatología depresiva e insatisfacción corporal, y menor autoestima. Consideramos que un abordaje específico sobre el perfeccionismo podría redundar en una mejoría psicopatológica de estos pacientes