BackgroundThe genetic variation underlying atorvastatin (ATV) pharmacokinetics was evaluated in a Mexican population. Aims of this study were: 1) to reveal the frequency of 87 polymorphisms in 36 genes related to drug metabolism in healthy Mexican volunteers, 2) to evaluate the impact of these polymorphisms on ATV pharmacokinetics, 3) to classify the ATV metabolic phenotypes of healthy volunteers, and 4) to investigate a possible association between genotypes and metabolizer phenotypes.MethodsA pharmacokinetic study of ATV (single 80-mg dose) was conducted in 60 healthy male volunteers. ATV plasma concentrations were measured by high-performance liquid chromatography mass spectrometry. Pharmacokinetic parameters were calculated by the non-compartmental method. The polymorphisms were determined with the PHARMAchip® microarray and the TaqMan® probes genotyping assay.ResultsThree metabolic phenotypes were found in our population: slow, normal, and rapid. Six gene polymorphisms were found to have a significant effect on ATV pharmacokinetics: MTHFR (rs1801133), DRD3 (rs6280), GSTM3 (rs1799735), TNFα (rs1800629), MDR1 (rs1045642), and SLCO1B1 (rs4149056). The combination of MTHFR, DRD3 and MDR1 polymorphisms associated with a slow ATV metabolizer phenotype.ConclusionFurther studies using a genetic preselection method and a larger population are needed to confirm these polymorphisms as predictive biomarkers for ATV slow metabolizers.Trial registrationAustralian New Zealand Clinical Trials Registry: ACTRN12614000851662, date registered: August 8, 2014.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2062-2) contains supplementary material, which is available to authorized users.

Psoriasis is a complex genetic disease, which has previously been associated with numerous single nucleotide polymorphisms (SNPs) that are implicated in various processes, including skin barrier functions and in the regulation of inflammatory and immune responses. The present study aimed to investigate the genotypic and allelic frequencies of 32 SNPs at 24 genetic loci, and their association with psoriasis in a Mexican population. These SNPs, which were associated with psoriasis in previous studies, included the following genes: Major histocompatibility complex class I-C (HLA-C), interleukin (IL)-12B, IL-23R, IL-23A, IL-28RA, tumor necrosis factor (TNF)-α, ring finger protein-114 (RNF114), cyclin-dependent kinase 5 regulatory subunit-associated protein 1-like 1, late cornified envelope 3B/3C, signal transducer and activator of transcription 4, LINC01185, interferon induced with helicase C domain 1, IL-13, TNF-α-induced protein 3 (TNFAIP3), TNFAIP3 interacting protein 1, endoplasmic reticulum aminopeptidase 1, TNF receptor-associated factor interacting protein 2, Leptin, nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor-alpha, F-box and leucine-rich repeat protein 19, nitric oxide synthase 2, cluster of differentiation 40, nuclear receptor coactivator 5, and ADAM metallopeptidase domain 33. A total of 32 male and 14 female subjects with a clinical diagnosis of chronic plaque psoriasis, as well as 103 control subjects, were analyzed. Molecular analyses were performed using TaqMan® assays in a TaqMan® OpenArray® Genotyping system. Results were analyzed using the Golden Helix SNP and Variation Suite 7 program. Of the 32 SNPs, six were associated with an increased risk of developing psoriasis, including: HLA-C rs10484554 [allele T: odds ratio (OR) 3.51], IL-12B rs3212227 (allele T: OR 1.88), IL-12B rs3213094 (allele C: OR 1.94), HLA complex group 27 rs1265181 (allele C: OR 2.83), annexin A6 rs17728338 (allele A: OR 2.41), and RNF114 rs6125829 (allele G: OR 1.98). Fisher's exact test detected statistical significance; however, following false discovery rate and Bonferroni correction, this association was no longer significant (threshold for genome-wide significance, P<1.56×10−3). SNPs that were associated with an increased risk of psoriasis in the present study have previously been associated with psoriasis in European, American, and Asian populations. In order to establish genome-wide significance, future studies must analyze a greater sample size. To the best of our knowledge, the present pilot study is the first to investigate the association between these 32 SNPs and psoriasis in a Mexican Mestizo population.

Due to the high toxicity and side effects of the use of traditional chemotherapy in cancer, scientists are working on the development of alternative therapeutic technologies. An example of this is the use of death‑induced gene therapy. This therapy consists of the killing of tumor cells via transfection with plasmid DNA (pDNA) that contains a gene which produces a protein that results in the apoptosis of cancerous cells. The cell death is caused by the direct activation of apoptosis (apoptosis‑induced gene therapy) or by the protein toxic effects (toxin‑induced gene therapy). The introduction of pDNA into the tumor cells has been a challenge for the development of this therapy. The most recent implementation of gene vectors is the use of polymeric or inorganic nanoparticles, which have biological and physicochemical properties (shape, size, surface charge, water interaction and biodegradation rate) that allow them to carry the pDNA into the tumor cell. Furthermore, nanoparticles may be functionalized with specific molecules for the recognition of molecular markers on the surface of tumor cells. The binding between the nanoparticle and the tumor cell induces specific endocytosis, avoiding toxicity in healthy cells. Currently, there are no clinical protocols approved for the use of nanoparticles in death‑induced gene therapy. There are still various challenges in the design of the perfect transfection vector, however nanoparticles have been demonstrated to be a suitable candidate. This review describes the role of nanoparticles used for pDNA transfection and key aspects for their use in death‑induced gene therapy.

We investigated whether likely pathogenic variants co-segregating with gastroschisis through a family-based approach using bioinformatic analyses were implicated in body wall closure. Gene Ontology (GO)/Panther functional enrichment and protein-protein interaction analysis by String identified several biological networks of highly connected genes in UGT1A3, UGT1A4, UGT1A5, UGT1A6, UGT1A7, UGT1A8, UGT1A9, UGT1A10, AOX1, NOTCH1, HIST1H2BB, RPS3, THBS1, ADCY9, and FGFR4. SVS–PhoRank identified a dominant model in OR10G4 (also as heterozygous de novo), ITIH3, PLEKHG4B, SLC9A3, ITGA2, AOX1, and ALPP, including a recessive model in UGT1A7, UGT1A6, PER2, PTPRD, and UGT1A3. A heterozygous compound model was observed in CDYL, KDM5A, RASGRP1, MYBPC2, PDE4DIP, F5, OBSCN, and UGT1A. These genes were implicated in pathogenetic pathways involving the following GO related categories: xenobiotic, regulation of metabolic process, regulation of cell adhesion, regulation of gene expression, inflammatory response, regulation of vascular development, keratinization, left-right symmetry, epigenetic, ubiquitination, and regulation of protein synthesis. Multiple background modifiers interacting with disease-relevant pathways may regulate gastroschisis susceptibility. Based in our findings and considering the plausibility of the biological pattern of mechanisms and gene network modeling, we suggest that the gastroschisis developmental process may be the consequence of several well-orchestrated biological and molecular mechanisms which could be interacting with gastroschisis predispositions within the first ten weeks of development.

Our findings suggest that gastroschisis may result from the interaction of several chromosomal regions in an additive manner as a pool of candidate genes were identified from critical regions supporting a role for vascular disruption, thrombosis, and mesodermal deficiency in the pathogenesis of gastroschisis.

Biotransformation is an enzyme-catalyzed process in which the body converts endogenous compounds, xenobiotics and toxic substances into harmless or easily excreted metabolites. The biotransformation reactions are classified as phase I and II reactions. Uridine 5'-diphospho (UDP)-glucuronosyltransferases (UGTs) are a superfamily of phase II enzymes which have roles in the conjugation of xenobiotics or endogenous compounds, including drugs and bilirubin, with glucuronic acid to make them easier to excrete. The method the human body uses to achieve glucuronidation may be affected by a large interindividual variation due to changes in the sequences of the genes encoding these enzymes. In the last five years, the study of the genetic variants of the UGTs at a molecular level has become important due to its association with several diseases and the ability to predict adverse events due to drug metabolism. In the present review, the structure and the prominent genetic variants of the UGT1A subfamily and their metabolic and clinical implications are described.

Abstract. The aim of the present study was to investigate whether genetic markers considered risk factors for metabolic syndromes, including dyslipidemia, obesity and type 2 diabetes mellitus (T2DM), can be applied to a Northeastern Mexican population. A total of 37 families were analyzed for 63 single nucleotide polymorphisms (SNPs), and the age, body mass index (BMI), glucose tolerance values and blood lipid levels, including those of cholesterol, low-density lipoprotein (LDL), very LDL (VLDL), high-density lipoprotein (HDL) and triglycerides were evaluated. Three genetic markers previously associated with metabolic syndromes were identified in the sample population, including KCNJ11, TCF7L2 and HNF4A. The KCNJ11 SNP rs5210 was associated with T2DM, the TCF7L2 SNP rs11196175 was associated with BMI and cholesterol and LDL levels, the TCF7L2 SNP rs12255372 was associated with BMI and HDL, VLDL and triglyceride levels, and the HNF4A SNP rs1885088 was associated with LDL levels (P<0.05).

Nanotechnology is revolutionizing the development of different branches of science. The investigation of nanomaterials in the battle against cancer is not an exception. The main goal of this contribution is to bring an overview about the types of organic and inorganic nanomaterials that are under investigation for its applications in different aspects of cancer therapy: detection, diagnosis, contrast agents, controlled drug delivery, and hyperthermia. This review also includes fundamental aspects such as basic properties and synthesis of nanoparticles, with an emphasis on the use of selfassembed systems such as micelles, microemulsions, nanoemulsions, and liposomes.