Association of CYP3A5 polymorphisms and parathyroid hormone with blood level of tacrolimus in patients with end-stage renal disease.
Association of CYP3A5 polymorphisms and parathyroid hormone with blood level of tacrolimus in patients with end-stage renal disease.
复制标题
终末期肾病患者CYP3A5基因多态性和甲状旁腺激素与他克莫司血药浓度的关系
DOI：
10.1111/cts.13065
复制
发表时间：
2021-09
期刊：
影响因子：
--
通讯作者：
Itoh H
中科院分区：
文献类型：
--
作者：
Tanaka R;Suzuki Y;Watanabe H;Fujioka T;Hirata K;Shin T;Ando T;Ono H;Tatsuta R;Mimata H;Maruyama T;Itoh H
由于他克莫司主要通过CYP 3A代谢，因此血药浓度/剂量（C/D）比受CYP 3A 5多态性的影响。继发性甲状旁腺功能亢进患者的甲状旁腺激素（PTH）表达增加，常与终末期肾病相关。最近，PTH已被证明在mRNA水平下调CYP 3A的表达。在这项研究中，我们检查了CYP 3A 5多态性对肾移植前终末期肾病患者血清全段甲状旁腺激素（iPTH）水平与他克莫司血药浓度的影响和相关性。对48例符合选择标准的患者进行了分析。受试者分为两个表型亚组：CYP 3A 5表达者（CYP 3A 5 *1/*1和 *1/*3; n = 15）和CYP 3A 5非表达者（CYP 3A 5 *3/*3; n = 33）。CYP 3A 5表达者的血他克莫司C/D（单位体重）比值显著低于CYP 3A 5非表达者。发现他克莫司C/D与iPTH浓度之间存在显著正相关性（r = 0.305，p = 0.035），排除20例同时给予CYP 3A抑制剂或诱导剂的患者后，相关系数更高（r = 0.428，p = 0.023）。逐步选择的多元Logistic回归分析确定CYP 3A 5多态性和血清iPTH水平是他克莫司C/D的显著相关因素。这些结果可能表明，在肾移植患者中使用他克莫司时，剂量设计的重要性不仅要考虑CYP 3A 5表型，还要考虑血清iPTH水平。
Because tacrolimus is predominantly metabolized by CYP3A, the blood concentration/dose (C/D) ratio is affected by CYP3A5 polymorphism. Parathyroid hormone (PTH) expression increases in secondary hyperparathyroidism, which is frequently associated with end‐stage renal disease. Recently, PTH has been shown to downregulate CYP3A expression at mRNA level. In this study, we examined the influence of CYP3A5 polymorphism on and association of serum intact‐PTH (iPTH) level with blood tacrolimus concentration in patients with end‐stage renal disease just before kidney transplantation. Forty‐eight patients who satisfied the selection criteria were analyzed. Subjects were classified into two phenotype subgroups: CYP3A5 expressor (CYP3A5*1/*1 and *1/*3; n = 15) and CYP3A5 nonexpressor (CYP3A5*3/*3; n = 33). The blood tacrolimus C/D (per body weight) ratio was significantly lower in CYP3A5 expressors than that in CYP3A5 nonexpressors. A significant positive correlation was found between tacrolimus C/D and iPTH concentrations (r = 0.305, p = 0.035), and the correlation coefficient was higher after excluding 20 patients co‐administered CYP3A inhibitor or inducer (r = 0.428, p = 0.023). A multiple logistic regression analysis by stepwise selection identified CYP3A5 polymorphism and serum iPTH level as significant factors associated with tacrolimus C/D. These results may suggest the importance of dose design considering not only the CYP3A5 phenotype but also serum iPTH level when using tacrolimus in patients who undergo renal transplantation.
登录
查看更多内容
影响因子：
6.7
作者：
通讯作者：
--
DOI：
10.2215/cjn.08020715
发表时间：
2016-04-01
影响因子：
9.8
作者：
Gutierrez, Orlando M.;Parsa, Afshin;Wolf, Myles
通讯作者：
Wolf, Myles
影响因子：
19.6
作者：
Fukagawa, Masafumi;Shimazaki, Ryutaro;Akizawa, Tadao
通讯作者：
Akizawa, Tadao
影响因子：
2.9
作者：
Niioka, Takenori;Kagaya, Hideaki;Satoh, Shigeru
通讯作者：
Satoh, Shigeru
影响因子：
6.7
作者：
Nolin, T. D.;Naud, J.;Pichette, V.
通讯作者：
Pichette, V.