Acetylation polymorphism expression in patients before and after liver transplantation: influence of host/graft genotypes.
The consequences of liver transplantation on NAT2 activity were studied in 58 patients of Caucasian origin and compared with a group control of 119 unrelated healthy individuals of the same ethnic origin. Acetylation phenotypes were determined using caffeine as a probe drug before and repeatedly after liver transplantation. NAT2 genotypes were determined with three separate polymerase chain reactions to detect either the NAT2*4 wild-type allele or the NAT2*5A, NAT2*6A and NAT2*7A mutated alleles, associated with a decrease in NAT2 enzyme activity. In patients, the molar urinary elimination ratio AFMU/(AFMU+1X+1U) appeared more reliable than AFMU/1X for assessing the acetylation phenotype and fitted better with the various haplotypes. The variation of xanthine oxidase activity as measured by the 1U/1X urinary elimination ratio, appeared to be responsible for the poor phenotype prediction from the AFMU/1X ratio in post-transplanted patients. Regardless of the pathologic conditions of the treatment in progress, the genotype of the liver played an overwhelming role in the phenotypic expression of NAT2 compared with the genotype of other organs, where NAT2 was expressed in patients who presented a chimerism after liver transplantation.
Service de Pharmacologie Clinique, CHU, Besançon, France.
E K
EK
Bendriss
Y C
YC
Bechtel
G
G
Paintaud
M P
MP
Brientini
G
G
Mantion
J P
JP
Miguet
A
A
Bennani
P R
PR
Bechtel
D000107:Acetylation; D000328:Adult; D000368:Aged; D000483:Alleles; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D002110:Caffeine / Q000493:pharmacokinetics; D005260:Female; D005838:Genotype; D006801:Humans; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic; D018183:Transplantation Chimera / Q000235:genetics*; D014969:Xanthine Oxidase / Q000032:analysis
D002110:Caffeine; D014969:Xanthine Oxidase; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human