Influence of donor and recipient genotypes on CYP2D6 phenotype after liver transplantation: a study of mutations CYP2D6*3 and CYP2D6*4.
OBJECTIVE
After liver transplantation (LT), genotypic differences between the recipient and the transplanted liver, medications and post-LT complications may all affect drug metabolism. We have studied the effect of two CYP2D6 mutations in the donor and the recipient on post-LT CYP2D6 phenotype.


METHODS
The CYP2D6 phenotype was assessed in 48 patients before and after LT with debrisoquine or dextromethorphan. CYP2D6*3 (CYP2D6A) and CYP2D6*4 (CYP2D6B) mutations were detected in the donor and the recipient using polymerase chain reaction.


RESULTS
Before LT, 40 subjects were classified as extensive metabolisers (EM) and 8 as poor metabolisers (PM); after transplantation, 41 were EMs and 7 were PMs. Genotype and phenotype were in agreement in 100% of EMs and 40% of PMs. The low percentage of agreement in PMs could not be explained by severely altered liver function. The phenotype of 13 subjects was apparently changed by LT: 6 EMs became PMs and 7 PMs became EMs. All four subjects in whom genotype changed following LT had a corresponding change in phenotype: two EM subjects became PMs and two PM subjects became EMs.


CONCLUSIONS
The low percentage of agreement in PMs may be partly explained by mutations other than CYP2D6*3 and CYP2D6*4. Nevertheless, our study shows that the CYP2D6 genotype of the donor controls the phenotype of the recipient of a liver transplantation.
Monek
O
O
Service de Chirurgie Digestive et de Transplantation Hépatique, Hôpital Jean Minjoz, Besançon, France.
Paintaud
G
G
Bechtel
Y
Y
Miguet
J P
JP
Mantion
G
G
Bechtel
P R
PR
D000328:Adult; D000368:Aged; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics* / Q000378:metabolism; D003647:Debrisoquin / Q000378:metabolism; D003915:Dextromethorphan / Q000378:metabolism; D005260:Female; D005838:Genotype; D006801:Humans; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D012189:Retrospective Studies
D003915:Dextromethorphan; D019389:Cytochrome P-450 CYP2D6; D003647:Debrisoquin