Hospital Infantil de México Federico Gómez, Mexico City, Mexico.
Arch Med Res. 2012 May;43(4):283-7. doi: 10.1016/j.arcmed.2012.05.005. Epub 2012 Jun 13.
Variability in CYP3A5 expression associated with differences in tacrolimus bioavailability has been documented. The wild-type allele CYP3A51 expresses the functional protein, whereas the CYP3A53 allele is a splice variant with a premature stop codon and encodes a truncated nonfunctional protein. The aim of the study was to determine the frequency of CYP3A51 and CYP3A53 in 291 (124 adults, 167 pediatric) Mexican renal transplant recipients, evaluate the tacrolimus dose requirements by genotype and compare genotype frequency data with that of other populations.
We carried out a multicenter study. Patients were recruited from three institutions located in Mexico City. Genotyping of the CYP3A51 and CYP3A53 alleles was performed by direct DNA sequencing.
Eighteen patients (6.2%) were CYP3A511 homozygous carriers or functional protein expresser homozygous, 121 patients (41.6 %) were CYP3A513 were heterozygous carriers or heterozygous expressers, and 152 patients (52.2%) were CYP3A533 homozygous carriers or homozygous nonexpressers. There was a statistically significant difference in frequency of the functional and nonfunctional expresser phenotypes from those reported for Black and Caucasian, but not for South Asian populations. The CYP3A5 phenotype had a significant impact in tacrolimus bioavailability, as wild-type carriers required higher dosing compared to mutated carriers to achieve similar drug trough levels. Patients with CYP3A511 genotype had a median dose requirement of 0.16 mg/kg/day, CYP3A513 patients had a median tacrolimus dose of 0.13 mg/kg/day and CYP3A533 had a median dose of 0.07 mg/kg/day (Kruskal-Wallis, p <0.0001).
Of the Mexican transplant recipients, 52.2% were CYP3A533 and required significantly lower tacrolimus dose than those with CYP3A5*1 allele.
已有研究证明，CYP3A5 表达的差异与他克莫司生物利用度的差异有关。野生型等位基因 CYP3A51 表达有功能的蛋白，而 CYP3A53 等位基因是一种剪接变异体，具有提前终止密码子，编码无功能的截断蛋白。本研究的目的是确定 291 例（124 例成人，167 例儿科）墨西哥肾移植受者 CYP3A51 和 CYP3A53 的频率，评估基因型与他克莫司剂量需求的关系，并将基因型频率数据与其他人群进行比较。
我们进行了一项多中心研究。患者来自墨西哥城的三家机构。通过直接 DNA 测序对 CYP3A51 和 CYP3A53 等位基因进行基因分型。
18 例患者（6.2%）为 CYP3A511 纯合子或功能性蛋白纯合子携带者，121 例患者（41.6%）为 CYP3A513 杂合子或杂合子表达者，152 例患者（52.2%）为 CYP3A533 纯合子或纯合子非表达者。功能性和非功能性表达表型的频率与黑人和白种人报道的频率有统计学显著差异，但与南亚人群没有差异。CYP3A5 表型对他克莫司生物利用度有显著影响，野生型携带者需要更高的剂量才能达到相似的药物谷浓度。CYP3A511 基因型患者的中位剂量需求为 0.16mg/kg/天，CYP3A513 患者的中位他克莫司剂量为 0.13mg/kg/天，CYP3A533 患者的中位剂量为 0.07mg/kg/天（Kruskal-Wallis，p<0.0001）。
在墨西哥的移植受者中，52.2%为 CYP3A533，需要的他克莫司剂量明显低于 CYP3A5*1 等位基因。
