Hipercolesterolemia y el polimorfismo del gen SR-B1

Cardiovascular disease is the leading cause of death in the world. The onset of these cardiovascular diseases depends on genetic and environmental factors, where lipid abnormalities, especially dyslipidemia, have a high prevalence in adulthood related to increased obesity and metabolic syndrome. In this sense, the SR-B1 receptor plays an important role in the purification of cholesterol and the selective absorption of HDL located mainly in the liver and also in steroid tissues, by apo A-I, and cholesterol ester are transported in a selective to cells, Although the particle itself, even apo A-I, is not captured by the tissues, but about cholesterol leaving the cells through HDL, which is then carried to the liver for excretion by bile. The aim of this article is to review the current knowledge of the possible association between hypercholesterolemia and 3 polymorphisms (Single Nucleotide Polimorphism; SNP), of the SR-B1 or SCARB1 gene, located on chromosome 12: the SNP’s of exon 1, intron 5 and exon 8.Las enfermedades cardiovasculares son la primera causa de muerte alrededor del mundo. Su aparición depende de factores genéticos y ambientales, donde, las anomalías lipídicas, específicamente las dislipidemias, presentan elevada prevalencia en la edad adulta relacionadas al incremento de la obesidad y síndrome metabólico. En este sentido, el receptor SR-B1  lleva acabo un papel importante en la depuración del colesterol y la captación selectiva de lipoproteínas de alta densidad (HDL) localizadas mayoritariamente en el hígado y en tejidos esteroidogénicos, a través de la apolipoproteina-A (apo A-I) y el colesterol éster, se lleva de manera mas selectiva en las células, se sabe que la apo A-I, no es captada por parte de los tejidos, sino,  por el colesterol que sale de las células a través de la HDL, que enseguida es llevado hacia el hígado para su excreción mediante la bilis. El objetivo del presente artículo es revisar el conocimiento actual de la posible asociación entre la hipercolesterolemia y 3 polimorfismos (Single Nucleótide Polimorphism; SNP), del gen SR-B1 o SCARB1, localizado en el cromosoma 12: los SNP’s del exón 1, del intrón 5 y en el exón 8

Asociación de las dislipidemias con el SNP rs5888 (exón 8) del gen SR-B1

Cardiovascular diseases (CVD) are the leading cause of death from non-communicable diseases in the world, with dyslipidemia appearing as a frequent irregularity and main risk factor. The SCARB1 gene encodes the SR-B1 receptor, which is involved in cholesterol clearance and selective HDL uptake. SR-B1 overexpression decreases HDL-C and atherosclerosis, while its absence increases HDL-C and increases atherosclerosis. Aim. To identify the type of association of dyslipidemias with the rs5888 SNP of the SRB1 gene (exon 8) in an apparently healthy population from the state of Morelos, Mexico. Methodology. From a total of 258 samples, DNA was extracted for its purification and quantification, then exon 8 was genotyped using real-time PCR and using the applied biosystems software, genotypic associations (with SNPs and without SNPs) were performed using the Odds Ratio statistical test. Results. 72.87% of the studied population presented dyslipidemia, with hypoαlipoproteinemia being the most frequent, mostly in men (78.19%). A borderline protective association was found for hypoαlipoproteinemia in those with the rs5888 SNP and a risk association for hypercholesterolemia and hypertriglyceridemia, concluding that a change in the same gene may increase or decrease the probability of developing cardiovascular diseases.Las enfermedades cardiovasculares (ECV) son la primera causa de muerte de las enfermedades no transmisibles en el mundo, figurando las dislipidemias como una irregularidad frecuente y principal factor de riesgo. El gen SCARB1 codifica el receptor SR-B1, el cual participa en la depuración del colesterol y captación selectiva de HDL. La sobre expresión del SR-B1 disminuye el HDL-C y la aterosclerosis, mientras que su ausencia incrementa el HDL-C y eleva la aterosclerosis. Objetivo. Identificar el tipo de asociación de las dislipidemias con el SNP rs5888 del gen SRB1 (exón 8) en población aparentemente sana del estado de Morelos México. Metodología. De un total de 258 muestras, se extrajo ADN para su purificación y cuantificación, posteriormente se realizó la genotipificación del exón 8 mediante PCR en tiempo real y utilizando el software applied biosystems, las asociaciones genotípicas (con SNP y sin SNP) se realizaron por la prueba estadística de Razón de Momios. Resultados. El 72.87 % de la población estudiada presenta dislipidemias, siendo la hipoαlipoproteinemia la más frecuente, mayormente en hombres (78.19 %). Se encontró asociación protectora limítrofe para hipoαlipoproteinemia quienes presenten el SNP rs5888 y asociación de riesgo en hipercolesterolemia e hipertrigliceridemia, concluyendo que un cambio en el mismo gen, pueden aumentar o disminuir la probabilidad de desarrollar enfermedades cardiovasculares

Towards precision medicine: defining and characterizing adipose tissue dysfunction to identify early immunometabolic risk in symptom-free adults from the GEMM family study

Interactions between macrophages and adipocytes are early molecular factors influencing adipose tissue (AT) dysfunction, resulting in high leptin, low adiponectin circulating levels and low-grade metaflammation, leading to insulin resistance (IR) with increased cardiovascular risk. We report the characterization of AT dysfunction through measurements of the adiponectin/leptin ratio (ALR), the adipo-insulin resistance index (Adipo-IRi), fasting/postprandial (F/P) immunometabolic phenotyping and direct F/P differential gene expression in AT biopsies obtained from symptom-free adults from the GEMM family study. AT dysfunction was evaluated through associations of the ALR with F/P insulin-glucose axis, lipid-lipoprotein metabolism, and inflammatory markers. A relevant pattern of negative associations between decreased ALR and markers of systemic low-grade metaflammation, HOMA, and postprandial cardiovascular risk hyperinsulinemic, triglyceride and GLP-1 curves was found. We also analysed their plasma non-coding microRNAs and shotgun lipidomics profiles finding trends that may reflect a pattern of adipose tissue dysfunction in the fed and fasted state. Direct gene differential expression data showed initial patterns of AT molecular signatures of key immunometabolic genes involved in AT expansion, angiogenic remodelling and immune cell migration. These data reinforce the central, early role of AT dysfunction at the molecular and systemic level in the pathogenesis of IR and immunometabolic disorders

Deep Multi-OMICs and Multi-Tissue Characterization in a Pre- and Postprandial State in Human Volunteers: The GEMM Family Study Research Design

Cardiovascular disease (CVD) and type 2 diabetes (T2D) are increasing worldwide. This is mainly due to an unhealthy nutrition, implying that variation in CVD risk may be due to variation in the capacity to manage a nutritional load. We examined the genomic basis of postprandial metabolism. Our main purpose was to introduce the GEMM Family Study (Genetics of Metabolic Diseases in Mexico) as a multi-center study carrying out an ongoing recruitment of healthy urban adults. Each participant received a mixed meal challenge and provided a 5-hours’ time course series of blood, buffy coat specimens for DNA isolation, and adipose tissue (ADT)/skeletal muscle (SKM) biopsies at fasting and 3 h after the meal. A comprehensive profiling, including metabolomic signatures in blood and transcriptomic and proteomic profiling in SKM and ADT, was performed to describe tendencies for variation in postprandial response. Our data generation methods showed preliminary trends indicating that by characterizing the dynamic properties of biomarkers with metabolic activity and analyzing multi-OMICS data it could be possible, with this methodology and research design, to identify early trends for molecular biology systems and genes involved in the fasted and fed states