The A54T polymorphism in the FABP2 gene and its relationship with obesity

Introduction: Obesity is a complex, multifactorial, and mostly preventable disease affecting, along with overweight, more than a third of today’s world population. Variations in the nucleotide sequence of both metabolic and appetite control genes have been counted among these non-modifiable factors and are associated with BMI, lipidic profile, and abdominal circumference alterations. Methods: An analytical, non-experimental, and transversal research was done with the purpose to assess the presence of A54T polymorphism in the FABP gene in a sub-sample from the Maracaibo City Metabolic Syndrome Prevalence Study. Results: 154 individuals eight subjects were carriers of the A54Tpolymorphism, namely, a genotypic frequency of 5.19 %, with a sex distribution of 50 % for women (n=4) and 50 % (n=4) for men. In respect of alleles similarity degree, 75 % (n=6) were homozygous, and 25 % (n=2) were heterozygous. Obesity diagnosis throughout BMI was only present in 12.50 % (n=1) of the A54T carriers. Conversely, 25 % (n=2) of the carriers were overweighed; 50 % (n=4) were presented as normal-weight people; and only 12.50 % (n=1), in one underweighted person. Conclusion: As in many other studies, we do not find an association between Ala54Thr polymorphism and obesity. This result reinforces the fact of the multifactorial character of these diseases and a carrier state of this polymorphism is not necessarily to experience a higher obesity risk, at least, in our environment.La obesidad es una enfermedad compleja, multifactorial y en su mayor parte prevenible que afecta, a más de un tercio de la población mundial actual. Las variaciones en la secuencia de nucleótidos de los genes de control del metabolismo y del apetito se consideran hasta ahora como factores no modificables y se asocian con alteraciones del IMC, del perfil lipídico y de la circunferencia abdominal. Métodos: Se realizó una investigación analítica, no experimental y transversal con el propósito de evaluar la presencia del polimorfismo A54T en el gen FABP en una submuestra del Estudio de Prevalencia del Síndrome Metabólico de la Ciudad de Maracaibo. Resultados: De los 154 individuos de la submuestra ocho sujetos fueron portadores del polimorfismo A54T, es decir, una frecuencia genotípica de 5,19 %, con una distribución por sexo de 50 % para las mujeres (n=4) y 50 % (n=4) para los hombres. Con respecto al grado de similitud de los alelos, el 75 % (n=6) eran homocigotos y el 25 % (n=2) heterocigotos. El diagnóstico de obesidad a lo largo del IMC sólo estuvo presente en el 12,50 % (n=1) de los portadores de A54T. Por el contrario, el 25 % (n=2) de los portadores tenían sobrepeso; el 50 % (n=4) se presentaron como personas de peso normal; y sólo el 12,50 % (n=1) en la categoría de peso insuficiente. Conclusión: No se encontró una asociación entre el polimorfismo de Ala54Thr y la obesidad. Este resultado refuerza el carácter multifactorial de estas enfermedades y que un estado portador de este polimorfismo no es causa necesaria para padecer obesidad, al menos, en nuestro medio

Neprilysin: A Potential Therapeutic Target of Arterial Hypertension?

Arterial hypertension is the most prevalent chronic disease in the adult population of developed countries and it constitutes a significant risk factor in the development of cardiovascular disease, contributing to the emergence of many comorbidities, among which heart failure excels, a clinical syndrome that nowadays represents a major health problem with uncountable hospitalizations and the indolent course of which progressively worsens until quality of life decreases and lastly death occurs prematurely. In the light of this growing menace, each day more efforts are invested in the field of cardiovascular pharmacology, searching for new therapeutic options that allow us to modulate the physiological systems that appear among these pathologies. Therefore, in the later years, the study of natriuretic peptides has become so relevant, which mediate beneficial effects at the cardiovascular level such as diuresis, natriuresis, and decreasing cardiac remodeling; their metabolism is mediated by neprilysin, a metalloproteinase, widely expressed in the human and capable of catalyzing many substrates. The modulation of these functions has been studied by decades, giving room to Sacubitril, the first neprilysin inhibitor, which in conjunction with an angiotensin receptor blocker has provided a high efficacy and tolerability among patients with heart failure, for whom it has already been approved and recommended. Nonetheless, in the matter of arterial hypertension, significant findings have arisen that demonstrate the potential role that it will play among the pharmacological alternatives in the upcoming years

Metabolic Syndrome and Subclinical Hypothyroidism: A Type 2 Diabetes-Dependent Association

Introduction. Subclinical hypothyroidism (ScH) is an endocrine alteration that is related to cardiovascular risk factors, including those categorized as components of the Metabolic Syndrome (MS). However, findings in prior reports regarding an association between these alterations are inconsistent. The purpose of this study was to determine the relationship between both entities in adult subjects from Maracaibo City, Venezuela. Materials and Methods. The Maracaibo City Metabolic Syndrome Prevalence Study is a descriptive, cross-sectional study with random and multistage sampling. In this substudy, 391 individuals of both genders were selected and TSH, free T3, and free T4 tests were performed as well as a complete lipid profile, fasting glycaemia, and insulin blood values. ScH was defined according to the National Health and Nutrition Examination Survey (NHANES) criteria: high TSH (≥4.12mUI/L) and normal free T4 (0.9-1,9 ng/dL) in subjects without personal history of thyroid disease. MS components were defined according to IDF/AHA/NHLBI/WHF/IAS/IASO-2009 criteria. A multiple logistic regression analysis was used to assess the relationship between MS components and ScH diagnosis. Results. Of the evaluated population, 10.5% (n=41) was diagnosed with ScH, with a higher prevalence in women (female: 13.6% versus male: 7.7%; χ2=3.56, p=0.05). Likewise, 56.1% (n=23) of the subjects with ScH were diagnosed with MS (χ2=4.85; p=0.03), being hyperglycemia the main associated criterion (χ2=11.7; p=0.001). In multivariable analysis, it was observed that the relationship was exclusive with the presence of type 2 diabetes mellitus (T2DM) OR: 3.22 (1.14-9.14); p=0.03. Conclusion. The relationship between ScH and MS in our population is dependent on the presence of hyperglycemia, specifically T2DM diagnosis, findings that vary from those previously reported in Latin American subjects

Microbiota and Diabetes Mellitus: Role of Lipid Mediators

Diabetes Mellitus (DM) is an inflammatory clinical entity with different mechanisms involved in its physiopathology. Among these, the dysfunction of the gut microbiota stands out. Currently, it is understood that lipid products derived from the gut microbiota are capable of interacting with cells from the immune system and have an immunomodulatory effect. In the presence of dysbiosis, the concentration of lipopolysaccharides (LPS) increases, favoring damage to the intestinal barrier. Furthermore, a pro-inflammatory environment prevails, and a state of insulin resistance and hyperglycemia is present. Conversely, during eubiosis, the production of short-chain fatty acids (SCFA) is fundamental for the maintenance of the integrity of the intestinal barrier as well as for immunogenic tolerance and appetite/satiety perception, leading to a protective effect. Additionally, it has been demonstrated that alterations or dysregulation of the gut microbiota can be reversed by modifying the eating habits of the patients or with the administration of prebiotics, probiotics, and symbiotics. Similarly, different studies have demonstrated that drugs like Metformin are capable of modifying the composition of the gut microbiota, promoting changes in the biosynthesis of LPS, and the metabolism of SCFA

The sick adipose tissue : new insights into defective signaling and crosstalk with the myocardium

Adipose tissue (AT) biology is linked to cardiovascular health since obesity is associated with cardiovascular disease (CVD) and positively correlated with excessive visceral fat accumulation. AT signaling to myocardial cells through soluble factors known as adipokines, cardiokines, branched-chain amino acids and small molecules like microRNAs, undoubtedly influence myocardial cells and AT function via the endocrine-paracrine mechanisms of action. Unfortunately, abnormal total and visceral adiposity can alter this harmonious signaling network, resulting in tissue hypoxia and monocyte/macrophage adipose infiltration occurring alongside expanded intra-abdominal and epicardial fat depots seen in the human obese phenotype. These processes promote an abnormal adipocyte proteomic reprogramming, whereby these cells become a source of abnormal signals, affecting vascular and myocardial tissues, leading to meta-inflammation, atrial fibrillation, coronary artery disease, heart hypertrophy, heart failure and myocardial infarction. This review first discusses the pathophysiology and consequences of adipose tissue expansion, particularly their association with meta-inflammation and microbiota dysbiosis. We also explore the precise mechanisms involved in metabolic reprogramming in AT that represent plausible causative factors for CVD. Finally, we clarify how lifestyle changes could promote improvement in myocardiocyte function in the context of changes in AT proteomics and a better gut microbiome profile to develop effective, non-pharmacologic approaches to CVD

Epidemiologic Behavior of Obesity in the Maracaibo City Metabolic Syndrome Prevalence Study

Introduction: Obesity is a worldwide public health issue. Since the epidemiological behaviour of this disease is not well established in our country, the purpose of this study was to determinate its prevalence in the Maracaibo City, Zulia State- Venezuela. Materials and Methods: A cross-sectional study was undertaken using the data set from the Maracaibo City Metabolic Syndrome Prevalence Study. The sample consists of 2108 individuals from both genders and randomly selected: 1119 (53.09%) women and 989 (46.91%) men. The participants were interrogated for a complete clinical history and anthropometric measurements. To classify obesity, the WHO criteria for Body Mass Index (BMI), and Waist Circumference (WC) from the IDF/NHLBI/AHA/WHF/IAS/IASO-2009 (IDF-2009) and ATPIII statements were applied. Results: For BMI, obesity had an overall prevalence of 33.3% (n = 701), and according to gender women had 32.4% (n = 363) and men had 34.2% (n = 338). Overweight had a prevalence of 34.8% (n = 733), Normal weight had 29.8% (n = 629), and Underweight had 2.1% (n = 45). Adding Obesity and Overweight results, the prevalence of elevated BMI (.25 Kg/m2) was 68.1%. Using the IDF-2009 WC’s cut-off, Obesity had 74.2% prevalence, compared to 51.7% using the ATPIII parameters. Conclusions: These results show a high prevalence of abdominal obesity in our locality defined by the WHO, IDF-2009 and ATPIII criteria, which were not designed for Latin-American populations. We suggest further investigation to estimate the proper values according to ethnicity, genetic background and sociocultural aspects

Retinoblastoma: un enfoque molecular, clínico y terapéutico

El retinoblastoma es el tumor ocular maligno más frecuenteen los niños, producido por una mutación en el gen supresorde tumores Retinoblastoma 1 (RB1) del genoma decélulas retinianas. Se ha señalado que el retinoblastoma seorigina en la capa nuclear interna de la retina, sin embargo,al estudiar morfológicamente algunos ejemplares se hanhallado características de células fotorreceptoras, por lo queaún existe controversia sobre el tipo de célula que origina latumoración. El retinoblastoma es considerado una enfermedadautosómica dominante, en donde generalmente ambosalelos del gen RB1 se encuentran mutados, produciendoque pRb se inactive y genere alteraciones en el ciclo celular.Puede afectar uno o ambos ojos, siendo el signo más comúnla leucocoria. Tras la sospecha clínica, un oftalmólogo experimentadodebe realizar una oftalmoscopia indirecta con midriasiscompleta para localizar el tumor. Además, se puedenaplicar técnicas de imagen como el ultrasonido b-scan, latomografía computarizada, o la imagen por resonancia magnéticapara confirmar el diagnóstico y explorar la naturalezadel tumor. Recientemente, se ha establecido que la quimioreducciónseguida por la consolidación focal adyuvante, encombinación con la detección temprana, han contribuido alaumento de la supervivencia global y a una disminución dela morbilidad. La evolución del conocimiento de esta entidadtanto en los aspectos moleculares, clínicos, diagnósticos yterapéuticos han brindado - en los últimos años- un mejormanejo de los pacientes afectados con esta grave condició

Dyslipidemia: Genetics, lipoprotein lipase and HindIII polymorphism [version 2; referees: 2 approved]

The direct link between lipid metabolism alterations and the increase of cardiovascular risk are well documented. Dyslipidemias, including isolated high LDL-c or mixed dyslipidemia, such as those seen in diabetes (hypertriglyceridemia, high LDL-c or low HDL-c), correlate with a significant risk of cardiovascular and cerebrovascular disease worldwide.  This review analyzes the current knowledge concerning the genetic basis of lipid metabolism alterations, emphasizing lipoprotein lipase gene mutations and the HindIII polymorphism, which are associated with decreased levels of triglycerides and LDL-c, as well as higher levels of HDL-c. These patterns would be associated with decreased global morbidity and mortality, providing protection against cardiovascular and cerebrovascular diseases

Niveles séricos de Lp(a) y su comportamiento en el estado Zulia: 10 años de investigación

La Lipoproteína Lp(a) es considerada uno de los factores de riesgo independientes más importantes para el desarrollo de las enfermedades cardiovasculares. La mayoría de los estudios prospectivos realizados hasta la fecha han demostrado que la Lp(a) es un predictor útil del desarrollo de la enfermedad arterial coronaria y en consecuencia, del infarto de miocardio. Los primeros estudios realizados en Venezuela sobre la Lp(a) han sido llevados a cabo en el Estado Zulia y es durante estos 10 años de investigación que se ha logrado profundizar en el comportamiento epidemiológico de esta lipoproteína, comprobando que existen diferentes factores que pueden alterar la concentración de Lp(a) más allá de lo que frecuentemente se documenta en la mayoría de los estudios publicados hasta la fecha, donde se recalca que la concentración sérica de esta lipoproteína está en su mayor parte genéticamente determinada. En nuestra población, factores como el grado de actividad física, la raza, ciertos antecedentes familiares en niños y adolescentes, y la deprivación estrogénica están probablemente involucrados en la modificación de los niveles séricos de Lp(a).Lipoprotein Lp(a) is considered one of the most important independent risk factors for atherosclerotic cardiovascular disease. Most prospective studies to date have shown that Lp(a) is a useful predictor for the development of coronary artery disease and as result myocardial infarction. Early studies in Venezuela on the Lp(a) have been conducted in the state of Zulia and it is during these years of research that has been made to deep the epidemiological behavior of this lipoprotein, checking that there are different factors that can affect the Lp (a) concentration beyond what is often documented in most published studies, which stresses that the serum concentration of this lipoprotein is largely genetically determined. In our population, factors such as levels of physical activity, race, family history in children and adolescents, and estrogen deprivation has been involved in a significant change in serum levels of Lp (a)