RESUMEN
Pharmacogenetic testing is becoming more common; however, very few quality control and other reference materials that cover alleles commonly included in such assays are currently available. To address these needs, the Centers for Disease Control and Prevention's Genetic Testing Reference Material Coordination Program, in collaboration with members of the pharmacogenetic testing community and the Coriell Cell Repositories, have characterized a panel of 107 genomic DNA reference materials for five loci (CYP2D6, CYP2C19, CYP2C9, VKORC1, and UGT1A1) that are commonly included in pharmacogenetic testing panels and proficiency testing surveys. Genomic DNA from publicly available cell lines was sent to volunteer laboratories for genotyping. Each sample was tested in three to six laboratories using a variety of commercially available or laboratory-developed platforms. The results were consistent among laboratories, with differences in allele assignments largely related to the manufacturer's assay design and variable nomenclature, especially for CYP2D6. The alleles included in the assay platforms varied, but most were identified in the set of 107 DNA samples. Nine additional pharmacogenetic loci (CYP4F2, EPHX1, ABCB1, HLAB, KIF6, CYP3A4, CYP3A5, TPMT, and DPD) were also tested. These samples are publicly available from Coriell and will be useful for quality assurance, proficiency testing, test development, and research.
Asunto(s)
Hidrocarburo de Aril Hidroxilasas/genética , Citocromo P-450 CYP2D6/genética , Marcadores Genéticos , Glucuronosiltransferasa/genética , Oxigenasas de Función Mixta/genética , Farmacogenética , Alelos , Línea Celular , Citocromo P-450 CYP2C19 , Citocromo P-450 CYP2C9 , ADN/genética , Genoma Humano , Genotipo , Humanos , Patología Molecular/instrumentación , Patología Molecular/métodos , Farmacogenética/instrumentación , Farmacogenética/métodos , Vitamina K Epóxido ReductasasRESUMEN
OBJECTIVE: Other investigators have shown that reductions in active sodium pump units increase uterine contractility. Therefore, our goal was to determine whether uterine sodium pump abundance is decreased in mouse models of term and preterm labor. STUDY DESIGN: Mice were studied during the final one-third of pregnancy. Other pregnant mice had preterm labor induced with lipopolysaccharide and were studied at timed intervals thereafter. Uterine sodium pump alpha3-isoform messenger RNA and protein were measured. Data were analyzed by analysis of variance. RESULTS: Uterine sodium pump alpha3-isoform messenger RNA fell significantly from day 14 to day 18 and remained low on the day of birth. Uterine sodium pump alpha3-isoform protein levels decreased significantly also. In lipopolysaccharide-induced preterm labor, uterine sodium pump alpha3-isoform protein, but not messenger RNA, decreased significantly. CONCLUSION: Sodium pump alpha3-isoform protein levels decreased in uterus before term labor and lipopolysaccharide-induced preterm labor. These findings are similar to those in humans, which suggests that this mouse model may be useful in the study of the sodium pump in human pregnancy. Reductions in sodium pump number can increase uterine contractile force and may contribute to labor.
