Total and high molecular weight adiponectin have similar utility for the identification of insulin resistance

<p>Abstract</p> <p>Background</p> <p>Insulin resistance (IR) and related metabolic disturbances are characterized by low levels of adiponectin. High molecular weight adiponectin (HMWA) is considered the active form of adiponectin and a better marker of IR than total adiponectin. The objective of this study is to compare the utility of total adiponectin, HMWA and the HMWA/total adiponectin index (S_Aindex) for the identification of IR and related metabolic conditions.</p> <p>Methods</p> <p>A cross-sectional analysis was performed in a group of ambulatory subjects, aged 20 to 70 years, in Mexico City. Areas under the receiver operator characteristic (ROC) curve for total, HMWA and the S_Aindex were plotted for the identification of metabolic disturbances. Sensitivity and specificity, positive and negative predictive values, and accuracy for the identification of IR were calculated.</p> <p>Results</p> <p>The study included 101 men and 168 women. The areas under the ROC curve for total and HMWA for the identification of IR (0.664 <it>vs</it>. 0.669, <it>P </it>= 0.74), obesity (0.592 <it>vs</it>. 0.610, <it>P </it>= 0.32), hypertriglyceridemia (0.661 <it>vs</it>. 0.671, <it>P </it>= 0.50) and hypoalphalipoproteinemia (0.624 <it>vs</it>. 0.633, <it>P </it>= 0.58) were similar. A total adiponectin level of 8.03 μg/ml was associated with a sensitivity of 57.6%, a specificity of 65.9%, a positive predictive value of 50.0%, a negative predictive value of 72.4%, and an accuracy of 62.7% for the diagnosis of IR. The corresponding figures for a HMWA value of 4.25 μg/dl were 59.6%, 67.1%, 51.8%, 73.7% and 64.2%.</p> <p>The area under the ROC curve of the S_Aindex for the identification of IR was 0.622 [95% CI 0.554-0.691], obesity 0.613 [95% CI 0.536-0.689], hypertriglyceridemia 0.616 [95% CI 0.549-0.683], and hypoalphalipoproteinemia 0.606 [95% CI 0.535-0.677].</p> <p>Conclusions</p> <p>Total adiponectin, HMWA and the S_Aindex had similar utility for the identification of IR and metabolic disturbances.</p

Factors associated with postprandial lipemia and apolipoprotein A-V levels in individuals with familial combined hyperlipidemia

Peer reviewe

Molecular Characterization of the Lipid Genome-Wide Association Study Signal on Chromosome 18q11.2 Implicates HNF4A-Mediated Regulation of the TMEM241 GeneHighlights

We recently identified a locus on chromosome 18q11.2 for high serum triglycerides (TGs) in Mexicans. We hypothesize that the lead GWAS single nucleotide polymorphism (SNP) rs9949617, or its linkage disequilibrium (LD) proxies, regulate one of the 5 genes in the TG-associated region

Adipose Co-expression networks across Finns and Mexicans identify novel triglyceride-associated genes

BACKGROUND: High serum triglyceride (TG) levels is an established risk factor for coronary heart disease (CHD). Fat is stored in the form of TGs in human adipose tissue. We hypothesized that gene co-expression networks in human adipose tissue may be correlated with serum TG levels and help reveal novel genes involved in TG regulation. METHODS: Gene co-expression networks were constructed from two Finnish and one Mexican study sample using the blockwiseModules R function in Weighted Gene Co-expression Network Analysis (WGCNA). Overlap between TG-associated networks from each of the three study samples were calculated using a Fisher’s Exact test. Gene ontology was used to determine known pathways enriched in each TG-associated network. RESULTS: We measured gene expression in adipose samples from two Finnish and one Mexican study sample. In each study sample, we observed a gene co-expression network that was significantly associated with serum TG levels. The TG modules observed in Finns and Mexicans significantly overlapped and shared 34 genes. Seven of the 34 genes (ARHGAP30, CCR1, CXCL16, FERMT3, HCST, RNASET2, SELPG) were identified as the key hub genes of all three TG modules. Furthermore, two of the 34 genes (ARHGAP9, LST1) reside in previous TG GWAS regions, suggesting them as the regional candidates underlying the GWAS signals. CONCLUSIONS: This study presents a novel adipose gene co-expression network with 34 genes significantly correlated with serum TG across populations

A Systems Genetics Approach Implicates USF1, FADS3, and Other Causal Candidate Genes for Familial Combined Hyperlipidemia

We hypothesized that a common SNP in the 3' untranslated region of the upstream transcription factor 1 (USF1), rs3737787, may affect lipid traits by influencing gene expression levels, and we investigated this possibility utilizing the Mexican population, which has a high predisposition to dyslipidemia. We first associated rs3737787 genotypes in Mexican Familial Combined Hyperlipidemia (FCHL) case/control fat biopsies, with global expression patterns. To identify sets of co-expressed genes co-regulated by similar factors such as transcription factors, genetic variants, or environmental effects, we utilized weighted gene co-expression network analysis (WGCNA). Through WGCNA in the Mexican FCHL fat biopsies we identified two significant Triglyceride (TG)-associated co-expression modules. One of these modules was also associated with FCHL, the other FCHL component traits, and rs3737787 genotypes. This USF1-regulated FCHL-associated (URFA) module was enriched for genes involved in lipid metabolic processes. Using systems genetics procedures we identified 18 causal candidate genes in the URFA module. The FCHL causal candidate gene fatty acid desaturase 3 (FADS3) was associated with TGs in a recent Caucasian genome-wide significant association study and we replicated this association in Mexican FCHL families. Based on a USF1-regulated FCHL-associated co-expression module and SNP rs3737787, we identify a set of causal candidate genes for FCHL-related traits. We then provide evidence from two independent datasets supporting FADS3 as a causal gene for FCHL and elevated TGs in Mexicans

Type 2 Diabetes Variants Disrupt Function of SLC16A11 through Two Distinct Mechanisms

Type 2 diabetes (T2D) affects Latinos at twice the rate seen in populations of European descent. We recently identified a risk haplotype spanning SLC16A11 that explains ∼20% of the increased T2D prevalence in Mexico. Here, through genetic fine-mapping, we define a set of tightly linked variants likely to contain the causal allele(s). We show that variants on the T2D-associated haplotype have two distinct effects: (1) decreasing SLC16A11 expression in liver and (2) disrupting a key interaction with basigin, thereby reducing cell-surface localization. Both independent mechanisms reduce SLC16A11 function and suggest SLC16A11 is the causal gene at this locus. To gain insight into how SLC16A11 disruption impacts T2D risk, we demonstrate that SLC16A11 is a proton-coupled monocarboxylate transporter and that genetic perturbation of SLC16A11 induces changes in fatty acid and lipid metabolism that are associated with increased T2D risk. Our findings suggest that increasing SLC16A11 function could be therapeutically beneficial for T2D. Video Abstract [Figure presented] Keywords: type 2 diabetes (T2D); genetics; disease mechanism; SLC16A11; MCT11; solute carrier (SLC); monocarboxylates; fatty acid metabolism; lipid metabolism; precision medicin

Actualidad y prospectiva de la investigación científica en el Centro Universitario Amecameca de la Universidad Autónoma del Estado de México

Con responsabilidad, se organizó un programa cuya finalidad fuera publicitar con transparencia dichos avances, a través de un esfuerzo de rendición de cuentas a la comunidad inmediata, la universitaria, y a la comunidad abierta, la sociedad que la principal referencia para tal efecto. El programa se concretiza a través del presente libro, conformado con una inspiración de investigación multidisciplinaria; sin embargo, para llegar a tal fin, el reto es realizar el proceso de búsqueda y generación de conocimiento transitando hacia la colaboración de los cuerpos académicos, que puedan construir nuevos conocimientos fortalecidos por la convergencia de diferentes campos del saber. En consecuencia, la primera etapa de esta estrategia es la publicidad de los trabajos investigativos ejercidos, para hacer un balance al día, pero también proyectar el futuro de cada campo y área del conocimiento. La organización explicativa está organizada por tres bloques representativos del quehacer en la generación de conocimiento del Centro Universitario, un primer bloque centra el interés en las humanidades, educación y sustentabilidad; el segundo bloque lo integra la reflexión científica sobre la construcción democrática, derechos humanos y equidad de género; en el tercer segmento se destina a la seguridad alimentaria, salud pública y sistemas agropecuarios. La actualidad de la investigación eleva la producción lograda y lo que en el momento se encuentra en construcción y los alcances que produce para la docencia, la investigación misma, y para la sociedad en general. La prospectiva es un área que todos los capítulos desarrollan con el propósito de delinear los alcances innovadores por andar en teoría, metodología e incluso en los saberes mismo

Contribution of Known Genetic Risk Variants to Dyslipidemias and Type 2 Diabetes in Mexico: A Population-Based Nationwide Study

Dyslipidemias are common risk factors for the development of chronic disorders including type 2 diabetes (T2D). Over 100 associated loci have been identified but few reports have evaluated the population attributable fraction captured by them in population-based nationwide surveys. Therefore, we determined the population contribution of a set of known genetic risk variants to the development of dyslipidemias and T2D in Mexico. This study included 1665 participants from a Mexican National Health Survey carried out in the year 2000. It is a probabilistic complex sample survey of households, which comprises representative data at a national level. 103 previously reported SNPs associated with different dyslipidemias or T2D were genotyped and used to compute polygenic risk scores. We found that the previously known variants associated with dyslipidemias explain at most 7% of the total risk variance of lipid levels. In contrast, the known genetic risk component for T2D explained a negligible amount of variance (0.1%). Notably, variants derived from the Native-American ancestry have the strongest effect and contribute with a high proportion of the variance. These results support the need for additional studies aimed to identify specific genetic risk variants for Mexican population