Impact of genetic variation in CYP2C19, CYP2D6, and CYP3A4 on oxycodone and its metabolites in a large database of clinical urine drug tests.

Urine drug testing (UDT) is a tool for monitoring drug use, including oxycodone. While variation in cytochrome P450 (CYP) genes is known to alter oxycodone metabolism, its impact on UDT results of oxycodone and its metabolites has not been well-studied. Here, multivariate analysis was performed on retrospective UDT results of 90,379 specimens collected from 14,684 genotyped patients prescribed oxycodone.

Genetic Testing for Variants Identifies Patients at Risk of Prolonged Neuromuscular Blockade in Response to Succinylcholine.

Background: Genetic variants in the (butyrylcholinesterase) gene are associated with reduced BChE enzyme activity and prolonged post-succinylcholine neuromuscular blockade, which can lead to postanesthetic apnea and respiratory depression. Testing for BChE deficiency is usually performed by biochemical methods and is generally only offered to patients who have a personal or family history of prolonged post-succinylcholine neuromuscular blockade.

Purpose: Using a clinical test, we investigated the frequencies of genotypes that are associated with increased risk for prolonged post-succinylcholine neuromuscular blockade.

A Screening Test for in a Large United States Patient Cohort Identifies Broader Risk of Carbamazepine-Induced Adverse Events.

is strongly associated with life-threatening severe skin hypersensitivity reactions in patients treated with carbamazepine (CBZ) and structurally related medications. FDA-approved labeling recommends screening before CBZ therapy in patients of Asian ancestry. In this study, we aimed to (a) identify a direct method for screening , and (b) evaluate prevalence in a large cohort of United States patients.

Frequency of Alleles Including Structural Variants in the United States.

The gene encodes an enzyme important in the metabolism of many commonly used medications. Variation in is associated with inter-individual differences in medication response, and genetic testing is used to optimize medication therapy. This report describes a retrospective study of allele frequencies in a large population of 104,509 de-identified patient samples across all regions of the United States (US).

Developmental genetics of secretory vesicle acidification during Caenorhabditis elegans spermatogenesis.

Secretory vesicles are used during spermatogenesis to deliver proteins to the cell surface. In Caenorhabditis elegans, secretory membranous organelles (MO) fuse with the plasma membrane to transform spermatids into fertilization-competent spermatozoa. We show that, like the acrosomal vesicle of mammalian sperm, MOs undergo acidification during development.

SPE-39 family proteins interact with the HOPS complex and function in lysosomal delivery.

Yeast and animal homotypic fusion and vacuole protein sorting (HOPS) complexes contain conserved subunits, but HOPS-mediated traffic in animals might require additional proteins. Here, we demonstrate that SPE-39 homologues, which are found only in animals, are present in RAB5-, RAB7-, and RAB11-positive endosomes where they play a conserved role in lysosomal delivery and probably function via their interaction with the core HOPS complex. Although Caenorhabditis elegans spe-39 mutants were initially identified as having abnormal vesicular biogenesis during spermatogenesis, we show that these mutants also have disrupted processing of endocytosed proteins in oocytes and coelomocytes.