title: Genotypic screening of the main opiate-related polymorphisms in a cohort of 139 sickle cell disease patients.
abstract: Because no frequency data are available for the main opiate-related polymorphisms in sickle-cell disease (SCD) populations, we decided to perform such a genotyping in a cohort of 139 individuals. For pharmacodynamics,the OPRM1 A118G and the COMT G322A single nucleotide polymorphisms (SNPs) were chosen for their negative effects on the m receptors [1,2]. For pharmacokinetics [3], important SNPs for the CYP2D6 gene (codeine to morphine conversion) and for three genes involved in morphine elimination (namely CYP3A, UGT2B7, and ABCB1) were genotyped. The allelic frequencies of the OPRM1 and COMT SNPs appeared very low (0.01 to 0.05-no double mutant homozygous),as well as the proportion of CYP2D6 poor metabolizers (1.4%)and CYP3A wild-type (17.9%) which are associated with a low morphine exposure. On the contrary, up to 35% of SCD patients may have unfavorable ABCB1 and UGT2B7 genotypes for a good morphine exposure.Obviously, pharmacokinetic studies with precise phenotype/genotype correlations are required to draw definitive conclusions.
authors.affiliation: Unité de Pathologie Moléculaire du Globule Rouge (Centre de Référence des Thalassémies), Laboratoire de Biochimie et de Biologie Moléculaire, Hôpital Edouard Herriot, Hospices Civils and Université Claude Bernard-Lyon 1, Lyon, France. philippe.joly@chu-lyon.fr
authors.forename: Philippe
authors.initials: P
authors.lastname: Joly
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Gagnieu
authors.forename: Claire
authors.initials: C
authors.lastname: Bardel
authors.forename: Alain
authors.initials: A
authors.lastname: Francina
authors.forename: Corinne
authors.initials: C
authors.lastname: Pondarre
authors.forename: Cyril
authors.initials: C
authors.lastname: Martin
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000755:Anemia, Sickle Cell / Q000453:epidemiology / Q000235:genetics*; D001682:Biological Availability; D001711:Biotransformation / Q000235:genetics; D044383:Black People / Q000235:genetics; D002394:Catechol O-Methyltransferase / Q000235:genetics; D003061:Codeine / Q000493:pharmacokinetics; D015331:Cohort Studies; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics; D051544:Cytochrome P-450 CYP3A / Q000235:genetics; D004351:Drug Resistance / Q000235:genetics; D005820:Genetic Testing; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics; D006801:Humans; D009020:Morphine / Q000493:pharmacokinetics; D009294:Narcotics / Q000493:pharmacokinetics*; D020641:Polymorphism, Single Nucleotide; D017450:Receptors, Opioid, mu / Q000235:genetics; D044465:White People / Q000235:genetics
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D009294:Narcotics; C485764:OPRM1 protein, human; D017450:Receptors, Opioid, mu; D009020:Morphine; C104464:CYP3A protein, human; D019389:Cytochrome P-450 CYP2D6; D051544:Cytochrome P-450 CYP3A; D002394:Catechol O-Methyltransferase; C491474:UGT2B7 protein, human; D014453:Glucuronosyltransferase; D003061:Codeine