Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Department of Rheumatology and Clinical Immunology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
J Hum Genet. 2014 Feb;59(2):107-9. doi: 10.1038/jhg.2013.129. Epub 2013 Dec 19.
Although the association between CYP3A5 polymorphism and blood concentration of tacrolimus (TAC) in patients with solid organ transplantation was established, whether the association is also true in patients with connective tissue disease (CTD) who usually receive small amount of TAC is uncertain. Here, we performed a quantitative linear regression analysis to address the association between CYP3A5 and blood TAC concentration in patients with CTD. A total of 72 patients with CTD were recruited in the current study and genotyped for rs776746 in CYP3A5, which showed strong association with TAC concentration in patients with solid organ transplantation. The blood trough concentration of TAC after taking 3 mg per day was retrospectively obtained for each patient. As a result, allele A of rs776746 showed a significant association with a decreasing blood concentration of TAC (P=0.0038). Those who are carrying at least one copy of the A allele displayed decreased mean concentration of TAC by 31.0% compared with subjects with GG genotype. Rs776746 is associated with concentrations of TAC in patients with CTD.
虽然 CYP3A5 多态性与实体器官移植患者中环孢素（TAC）的血药浓度之间存在关联，但在通常接受小剂量 TAC 的结缔组织病（CTD）患者中，这种关联是否也成立尚不确定。在这里，我们进行了定量线性回归分析，以确定 CTD 患者中 CYP3A5 与 TAC 血药浓度之间的关系。本研究共招募了 72 例 CTD 患者，并对 CYP3A5 的 rs776746 进行了基因分型，该基因分型与实体器官移植患者 TAC 浓度有很强的关联。每位患者均回顾性地获得了每天服用 3mg 后 TAC 的血药谷浓度。结果表明，rs776746 的等位基因 A 与 TAC 血药浓度的降低有显著相关性（P=0.0038）。与 GG 基因型的受试者相比，携带至少一个 A 等位基因的患者 TAC 的平均浓度降低了 31.0%。rs776746 与 CTD 患者的 TAC 浓度相关。
