Genotypic screening of the main opiate-related polymorphisms in a cohort of 139 sickle cell disease patients

Philippe Joly; Marie-Claude Gagnieu; Claire Bardel; Alain Francina; Corinne Pondarre; Cyril Martin

doi:10.1002/ajh.23137

Genotypic screening of the main opiate-related polymorphisms in a cohort of 139 sickle cell disease patients

Am J Hematol. 2012 May;87(5):534-6. doi: 10.1002/ajh.23137. Epub 2012 Mar 19.

Authors

Philippe Joly¹, Marie-Claude Gagnieu, Claire Bardel, Alain Francina, Corinne Pondarre, Cyril Martin

Affiliation

¹ 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

PMID: 22430884
DOI: 10.1002/ajh.23137

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

ATP Binding Cassette Transporter, Subfamily B
ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
Anemia, Sickle Cell / epidemiology
Anemia, Sickle Cell / genetics*
Biological Availability
Biotransformation / genetics
Black People / genetics
Catechol O-Methyltransferase / genetics
Codeine / pharmacokinetics
Cohort Studies
Cytochrome P-450 CYP2D6 / genetics
Cytochrome P-450 CYP3A / genetics
Drug Resistance / genetics
Genetic Testing
Genotype
Glucuronosyltransferase / genetics
Humans
Morphine / pharmacokinetics
Narcotics / pharmacokinetics*
Polymorphism, Single Nucleotide*
Receptors, Opioid, mu / genetics
White People / genetics

Substances

ABCB1 protein, human
ATP Binding Cassette Transporter, Subfamily B
ATP Binding Cassette Transporter, Subfamily B, Member 1
Narcotics
OPRM1 protein, human
Receptors, Opioid, mu
Morphine
CYP3A protein, human
Cytochrome P-450 CYP2D6
Cytochrome P-450 CYP3A
Catechol O-Methyltransferase
UGT2B7 protein, human
Glucuronosyltransferase
Codeine