Genetic variants in SLC22A1 are related to serum lipid levels in Mexican women.

Dyslipidemia is the main risk factor for coronary artery disease and is characterized by alterations in concentrations of lipids, including low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), and triacylglycerols. The participation of several genes in the development of dyslipidemia has been evidenced. Genetic variants in SLC22A1 have been associated with elevated cholesterol and LDL-c levels. The aim of this study was to evaluate the association between single-nucleotide polymorphisms (SNPs) in the SLC22A1 gene with atherogenic risk lipid levels in Mexican women. Anthropometric and biochemical measurements were performed, and four SNPs in SLC22A1 were genotyped by real-time polymerase chain reaction. The Hardy-Weinberg equilibrium was verified, and haplotype frequencies were calculated. We found significant differences between the allele frequencies of the SNPs analyzed with those reported in Mexico and in the world, which could be due to differences in the historical admixture of the women studied. Generalized linear models were evaluated to determine the association between genotypes and haplotypes with lipids levels. We identified a significant increase in total cholesterol and LDL-c levels in women who were carriers of the GA and AG genotypes of the polymorphisms rs628031 and rs594709, respectively, significant effect that is also shown in a dominant inheritance model. Interestingly, we identified an important relationship of the AGC-GAT haplotype with the elevation in LDL-c levels and AGA-GAT haplotype with the elevation in HDL-c levels. On the other hand, we found a strong linkage disequilibrium between the polymorphisms studied. Our results show that variants in the SLC22A1 gene influence serum levels of atherogenic risk lipids, suggesting that these variants probably affect the function of organic cation transporter-1 and therefore, on the regulation of lipid metabolism.

Role of Long Non-Coding RNAs and the Molecular Mechanisms Involved in Insulin Resistance.

Long non-coding RNAs (lncRNAs) are single-stranded RNA biomolecules with a length of >200 nt, and they are currently considered to be master regulators of many pathological processes. Recent publications have shown that lncRNAs play important roles in the pathogenesis and progression of insulin resistance (IR) and glucose homeostasis by regulating inflammatory and lipogenic processes. lncRNAs regulate gene expression by binding to other non-coding RNAs, mRNAs, proteins, and DNA. In recent years, several mechanisms have been reported to explain the key roles of lncRNAs in the development of IR, including metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), imprinted maternal-ly expressed transcript (H19), maternally expressed gene 3 (MEG3), myocardial infarction-associated transcript (MIAT), and steroid receptor RNA activator (SRA), HOX transcript antisense RNA (HOTAIR), and downregulated Expression-Related Hexose/Glucose Transport Enhancer (DREH). LncRNAs participate in the regulation of lipid and carbohydrate metabolism, the inflammatory process, and oxidative stress through different pathways, such as cyclic adenosine monophosphate/protein kinase A (cAMP/PKA), phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT), polypyrimidine tract-binding protein 1/element-binding transcription factor 1c (PTBP1/SREBP-1c), AKT/nitric oxide synthase (eNOS), AKT/forkhead box O1 (FoxO1), and tumor necrosis factor-alpha (TNF-α)/c-Jun-N-terminal kinases (JNK). On the other hand, the mechanisms linked to the molecular, cellular, and biochemical actions of lncRNAs vary according to the tissue, biological species, and the severity of IR. Therefore, it is essential to elucidate the role of lncRNAs in the insulin signaling pathway and glucose and lipid metabolism. This review analyzes the function and molecular mechanisms of lncRNAs involved in the development of IR.

Dysregulation of lncRNA-H19 in cardiometabolic diseases and the molecular mechanism involved : a systematic review.

Introduction: Cardiometabolic diseases are a global public health problem, with significant increases in their prevalence. Different epigenetic factors involved in the progression of metabolic alterations have been described, such as long non-coding RNAs (lncRNAs). H19 is a multifunctional lncRNA expressed from the maternal allele, with low expression after birth, except in the skeletal muscle and heart. Recent studies have linked its dysregulation to alterations in cell metabolism.Areas covered: H19 plays a role in the pathogenesis of coronary artery disease, nonalcoholic fatty liver disease, hepatic and renal fibrosis, insulin resistance, type 2 diabetes, and inflammation. H19 acts mainly as a competitive endogenous RNA of molecules involved in pathways that regulate cell metabolism. In this review, we analyzed the dysregulation of H19 in cardiometabolic diseases and its relationship with molecular alterations in different signaling pathways.Expert opinion: The association of H19 with the development of cardiometabolic diseases, indicates that H19 could be a therapeutic target and prognostic biomarker for these diseases. Controversies have been reported regarding the expression of H19 in some metabolic diseases, therefore, it is necessary to continue research to clarify its pathogenic effect in different organs.

Altered levels of MALAT1 and H19 derived from serum or serum exosomes associated with type-2 diabetes.

Environmental, genetic and epigenetic risk factors have been closely related to the development of type-2 diabetes (T2D). It has been reported that the expression in H19 and MALAT1 are related to metabolic diseases. To analyze the relationship between the expression of H19 and MALAT1 lncRNAs with diabetic patients. A study was conducted in subjects with T2D and nondiabetic controls, residents of Mexico City. Anthropometric measurements were made, and serum concentrations of glucose, glycosylated hemoglobin, total cholesterol, triglycerides, high- and low-density lipoprotein cholesterol were analyzed. Total RNA was extracted from serum and serum exosomes. The H19 and MALAT1 expression levels were quantified by RT-qPCR. A significant reduction in the expression of MALAT1 from serum or serum exosomes were found in patients with T2D, metabolic syndrome and low levels of HDL-c. Significant increase in H19 levels was found in diabetic subjects with poor glycemic control. Additionally, the principal component analyzes showed that serum MALAT1 expression was associated with total cholesterol and HDL-c levels, and the exosomes H19 expression was associated with waist circumference. The results obtained suggest that MALAT1 expression levels could be an epigenetic biomarker of diabetes risk or of its comorbidities.

Analysis of admixture proportions in seven geographical regions of the state of Guerrero, Mexico.

OBJECTIVE: Mexico's current population structure has been defined by admixture between European, Native American, and to some extent African, groups that started in the sixteenth century. The aim of this research was to analyze the relative contributions of these continental population groups to the seven regions of the state of Guerrero, Mexico. METHODS: A total of 104 ancestry informative markers were analyzed in 480 unrelated women from the seven regions of the state of Guerrero. The individual ancestry proportions were estimated using the software ADMIXMAP v3.2. RESULTS: The relative Native American, European and African ancestral contributions to the whole sample were estimated to be 69%, 27%, and 1.9%, respectively. We observed significant differences in admixture proportions across the regions. The highest average Native American ancestry was found in the Montaña region and the lowest in Costa Grande. Conversely, the highest European contribution was observed in Costa Grande. The highest African contributions were observed in the regions of Costa Chica and Costa Grande. CONCLUSIONS: The genetic structure of the population of Guerrero reflects quite well the historical processes that have occurred in this state. Native American population settlements were mainly in the regions of Montaña, Norte, and Centro, where the highest indigenous genetic contribution is observed today. European settlers came from the center of the state to regions with significant agricultural and mining activities. The highest African contributions are observed in coastal regions, in agreement with historical evidence about slave trade routes in the Americas.

Polymorphisms in the LPL and CETP Genes and Haplotype in the ESR1 Gene Are Associated with Metabolic Syndrome in Women from Southwestern Mexico.

Metabolic syndrome (MetS) is a combination of metabolic disorders associated with an increased risk for cardiovascular disease (CVD). Studies in women reported associations between polymorphisms in ESR1, LPL and CETP genes and MetS. Our aim was to evaluate the association between variants in ESR1, LPL and CETP genes with MetS and its components. Four hundred and eighty women were analyzed, anthropometric features and biochemical profiles were evaluated, and genotyping was performed by real-time PCR. We found an association with elevated glucose levels (odds ratio (OR) = 2.9; p = 0.013) in carrying the AA genotype of rs1884051 in the ESR1 gene compared with the GG genotype, and the CC genotype of rs328 in the LPL gene was associated with MetS compared to the CG or GG genotype (OR = 2.8; p = 0.04). Moreover, the GA genotype of rs708272 in the CETP gene is associated with MetS compared to the GG or AA genotype (OR = 1.8; p = 0.006). In addition the ACTCCG haplotype in the ESR1 gene is associated with a decrease in the risk of MetS (OR = 0.02; p < 0.001). In conclusion, our results show the involvement of the variants of ESR1, LPL and CETP genes in metabolic events related to MetS or some of its features.