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Genotypic screening of the main opiate‐related polymorphisms in a cohort of 139 sickle cell disease patients
Author(s) -
Joly Philippe,
Gagnieu MarieClaude,
Bardel Claire,
Francina Alain,
Pondarre Corinne,
Martin Cyril
Publication year - 2012
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.23137
Subject(s) - genotype , single nucleotide polymorphism , genotyping , opiate , codeine , haplotype , medicine , pharmacogenetics , cyp2d6 , morphine , allele , allele frequency , cohort , ugt2b7 , pharmacology , genetics , biology , gene , receptor , glucuronidation , in vitro , microsome
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.