Bendriss E K, Bechtel Y C, Paintaud G, Brientini M P, Mantion G, Miguet J P, Bennani A, Bechtel P R
Service de Pharmacologie Clinique, CHU, Besançon, France.
Pharmacogenetics. 1998 Jun;8(3):201-9. doi: 10.1097/00008571-199806000-00003.
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 NAT24 wild-type allele or the NAT25A, NAT26A and NAT27A 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.
在58名高加索裔患者中研究了肝移植对NAT2活性的影响，并与119名相同种族来源的无关健康个体组成的对照组进行比较。在肝移植前后，使用咖啡因作为探针药物来确定乙酰化表型。通过三个独立的聚合酶链反应确定NAT2基因型，以检测NAT24野生型等位基因或与NAT2酶活性降低相关的NAT25A、NAT26A和NAT27A突变等位基因。在患者中，摩尔尿排泄率AFMU/（AFMU+1X+1U）在评估乙酰化表型方面似乎比AFMU/1X更可靠，并且与各种单倍型更匹配。通过1U/1X尿排泄率测量的黄嘌呤氧化酶活性变化，似乎是导致移植后患者中AFMU/1X比值对表型预测不佳的原因。无论正在进行的治疗的病理状况如何，与其他器官的基因型相比，肝脏的基因型在NAT2的表型表达中起着压倒性的作用，在肝移植后出现嵌合体的患者中，其他器官也表达NAT2。
