ABSTRACT
Oseltamivir, a pro-drug, is the best option for treatment and chemoprophylaxis for influenza outbreaks. However, many patients treated with oseltamivir developed adverse reactions, including hypersensitivity, gastritis, and neurological symptoms. The aim of this study was to determine the adverse drug reactions (ADRs) in Mexican patients treated with oseltamivir and whether these ADRs are associated with SNPs of the genes involved in the metabolism, transport, and interactions of oseltamivir. This study recruited 310 Mexican patients with acute respiratory diseases and treated them with oseltamivir (75 mg/day for 5 days) because they were suspected to have influenza A/H1N1 virus infection. Clinical data were obtained from medical records and interviews. Genotyping was performed using real-time polymerase chain reaction and TaqMan probes. The association was assessed under genetic models with contingency tables and logistic regression analysis. Out of 310 patients, only 38 (12.25%) presented ADRs to oseltamivir: hypersensitivity (1.9%), gastritis (10%), and depression and anxiety (0.9%). The polymorphism ABCB1-rs1045642 was associated with adverse drug reactions under the recessive model (P = 0.017); allele C was associated with no adverse drug reactions, while allele T was associated with adverse drug reactions. The polymorphisms SLC15A1-rs2297322, ABCB1-rs2032582, and CES1-rs2307243 were not consistent with Hardy-Weinberg equilibrium, and no other associations were found for the remaining polymorphisms. In conclusion, the polymorphism rs1045642 in the transporter encoded by the ABCB1 gene is a potential predictive biomarker of ADRs in oseltamivir treatment.
Subject(s)
Antiviral Agents/metabolism , Drug-Related Side Effects and Adverse Reactions/genetics , Drug-Related Side Effects and Adverse Reactions/metabolism , Oseltamivir/metabolism , Polymorphism, Single Nucleotide/genetics , Respiration Disorders/genetics , Respiration Disorders/metabolism , Acute Disease , Adolescent , Adult , Antiviral Agents/adverse effects , Biological Transport/physiology , Child , Drug Interactions/physiology , Drug-Related Side Effects and Adverse Reactions/epidemiology , Female , Genetic Association Studies/methods , Humans , Influenza A Virus, H1N1 Subtype/isolation & purification , Influenza, Human/drug therapy , Influenza, Human/epidemiology , Influenza, Human/genetics , Influenza, Human/metabolism , Male , Mexico/epidemiology , Middle Aged , Oseltamivir/adverse effects , Protein Transport/physiology , Respiration Disorders/drug therapy , Respiration Disorders/epidemiology , Retrospective Studies , Young AdultABSTRACT
BACKGROUND: Acute respiratory distress syndrome (ARDS) is a potentially devastating form of acute inflammatory lung injury as well as a major cause of acute respiratory failure. Although researchers have made significant progresses in elucidating the pathophysiology of this complex syndrome over the years, the absence of a universal detail disease mechanism up until now has led to a series of practical problems for a definitive treatment. This study aimed to predict some genes or pathways associated with sepsis-related ARDS based on a public microarray dataset and to further explore the molecular mechanism of ARDS. RESULTS: A total of 122 up-regulated DEGs and 91 down-regulated differentially expressed genes (DEGs) were obtained. The up- and down-regulated DEGs were mainly involved in functions like mitotic cell cycle and pathway like cell cycle. Protein-protein interaction network of ARDS analysis revealed 20 hub genes including cyclin B1 (CCNB1), cyclin B2 (CCNB2) and topoisomerase II alpha (TOP2A). A total of seven transcription factors including forkhead box protein M1 (FOXM1) and 30 target genes were revealed in the transcription factor-target gene regulation network. Furthermore, co-cited genes including CCNB2-CCNB1 were revealed in literature mining for the relations ARDS related genes. CONCLUSIONS: Pathways like mitotic cell cycle were closed related with the development of ARDS. Genes including CCNB1, CCNB2 and TOP2A, as well as transcription factors like FOXM1 might be used as the novel gene therapy targets for sepsis related ARDS
Subject(s)
Humans , Respiration Disorders/genetics , Sepsis/complications , Sepsis/genetics , Genetic Association Studies , Transcriptome , Transcription Factors , Down-Regulation , Cell Cycle/genetics , Up-Regulation , Gene Targeting , Gene Expression Profiling , Databases, Genetic , Protein Interaction MapsABSTRACT
Cri du chat syndrome (CdCS) and primary ciliary dyskinesia (PCD) are rare diseases that present with frequent respiratory symptoms. PCD can be caused by hemizygous DNAH5 mutation in combination with a 5p segmental deletion attributable to CdCS on the opposite chromosome. Chronic oto-sino-pulmonary symptoms or organ laterality defects in CdCS should prompt an evaluation for PCD.
Subject(s)
Chromosomes, Human, Pair 5/genetics , Cri-du-Chat Syndrome/diagnostic imaging , Cri-du-Chat Syndrome/genetics , Kartagener Syndrome/diagnostic imaging , Kartagener Syndrome/genetics , Mutation , Axonemal Dyneins/genetics , Child , Chromosome Deletion , Chromosome Mapping , Codon , Female , Hemizygote , Humans , Male , Phenotype , Radiography , Respiration Disorders/diagnostic imaging , Respiration Disorders/geneticsABSTRACT
We observed the Joubert syndrome (JS) associated with bilateral morning glory disk anomaly and cystic dysplastic kidneys in three patients from a consanguineous kindred. Homozygosity mapping excluded three JS candidate loci as sites harboring the disease gene. We thus delineate an autosomal recessive disorder, distinct from JS and related conditions.