中华小儿外科杂志
中華小兒外科雜誌
중화소인외과잡지
CHINESE JOURNAL OF PEDIATRIC SURGERY
2014年
6期
452-456
,共5页
郑章强%朱志军%孙丽莹%曲伟%魏林%李代红%刘伟%巫强%隋晓军
鄭章彊%硃誌軍%孫麗瑩%麯偉%魏林%李代紅%劉偉%巫彊%隋曉軍
정장강%주지군%손려형%곡위%위림%리대홍%류위%무강%수효군
细胞色素P450%他克莫司结合蛋白质类%胆道闭锁%肝移植
細胞色素P450%他剋莫司結閤蛋白質類%膽道閉鎖%肝移植
세포색소P450%타극막사결합단백질류%담도폐쇄%간이식
Cytochrome P-450%Tacrolimus blinding proteins%Biliary atresia%Transplantation
目的 分析儿童活体肝移植中供受体CYP3A5基因多态性及其与患儿肝移植术后他克莫司浓度/剂量比的关系,为肝移植术后他克莫司的个体化用药提供可靠的参考指标,优化用药方案并减少不良反应.方法 收集本治疗组活体肝移植中供受体外周血标本,使用PCR-SSP法测定CYP3A5基因型,收集患儿术后他克莫司用药剂量以及血药浓度相关数据.根据受体基因型可将所有患儿分为受体表达组和受体非表达组,根据供体基因型可将所有患儿分为供体表达组和供体非表达组,根据供受体基因型分为3组:即供体非表达/受体非表达组、供体/受体单一表达组、供体表达/受体表达组,分别进行统计分析.结果 78例供受体中CYP3A5*3*3 47例(60.3％),CYP3A5*1*328例(35.9％),CYP3A5*1*1 3例(3.8％).受体基因表达组比受体基因非表达组术后1、2、4、8周C0/D明显更低,差异有统计学意义(P＜0.05);供体基因表达组比供体基因非表达组受体术后1、2、4周G0/D明显更低,差异有统计学意义(P＜0.05);供体非表达/受体非表达组术后第1、2、4、8周G0/D显著高于供体/受体单一表达组及供体表达/受体表达组,差异有统计学意义(P＜0.05);供体/受体单一表达组与供体表达/受体表达组相比术后1、2、4、8周C0/D差异均无统计学意义(P＞0.05).结论 供受体CYP3A5基因多态性与肝移植术后早期受体的他克莫司用药剂量及所达到的全血谷值浓度的个体化差异密切相关,在儿童活体肝移植中需要同时考虑供受体基因对受体术后他克莫司药代动力学的影响,要达到相同的血药浓度,供体/受体基因型中只要其中一方含有CYP3A5*1等位基因,术后所需的他克莫司剂量就会相应增加.分析供受体CYP3A5基因多态性可以为肝移植术后他克莫司的个体化用药提供可靠的参考指标,指导最佳的用药剂量,提高药效并减少不良反应.
目的 分析兒童活體肝移植中供受體CYP3A5基因多態性及其與患兒肝移植術後他剋莫司濃度/劑量比的關繫,為肝移植術後他剋莫司的箇體化用藥提供可靠的參攷指標,優化用藥方案併減少不良反應.方法 收集本治療組活體肝移植中供受體外週血標本,使用PCR-SSP法測定CYP3A5基因型,收集患兒術後他剋莫司用藥劑量以及血藥濃度相關數據.根據受體基因型可將所有患兒分為受體錶達組和受體非錶達組,根據供體基因型可將所有患兒分為供體錶達組和供體非錶達組,根據供受體基因型分為3組:即供體非錶達/受體非錶達組、供體/受體單一錶達組、供體錶達/受體錶達組,分彆進行統計分析.結果 78例供受體中CYP3A5*3*3 47例(60.3％),CYP3A5*1*328例(35.9％),CYP3A5*1*1 3例(3.8％).受體基因錶達組比受體基因非錶達組術後1、2、4、8週C0/D明顯更低,差異有統計學意義(P＜0.05);供體基因錶達組比供體基因非錶達組受體術後1、2、4週G0/D明顯更低,差異有統計學意義(P＜0.05);供體非錶達/受體非錶達組術後第1、2、4、8週G0/D顯著高于供體/受體單一錶達組及供體錶達/受體錶達組,差異有統計學意義(P＜0.05);供體/受體單一錶達組與供體錶達/受體錶達組相比術後1、2、4、8週C0/D差異均無統計學意義(P＞0.05).結論 供受體CYP3A5基因多態性與肝移植術後早期受體的他剋莫司用藥劑量及所達到的全血穀值濃度的箇體化差異密切相關,在兒童活體肝移植中需要同時攷慮供受體基因對受體術後他剋莫司藥代動力學的影響,要達到相同的血藥濃度,供體/受體基因型中隻要其中一方含有CYP3A5*1等位基因,術後所需的他剋莫司劑量就會相應增加.分析供受體CYP3A5基因多態性可以為肝移植術後他剋莫司的箇體化用藥提供可靠的參攷指標,指導最佳的用藥劑量,提高藥效併減少不良反應.
목적 분석인동활체간이식중공수체CYP3A5기인다태성급기여환인간이식술후타극막사농도/제량비적관계,위간이식술후타극막사적개체화용약제공가고적삼고지표,우화용약방안병감소불량반응.방법 수집본치료조활체간이식중공수체외주혈표본,사용PCR-SSP법측정CYP3A5기인형,수집환인술후타극막사용약제량이급혈약농도상관수거.근거수체기인형가장소유환인분위수체표체조화수체비표체조,근거공체기인형가장소유환인분위공체표체조화공체비표체조,근거공수체기인형분위3조:즉공체비표체/수체비표체조、공체/수체단일표체조、공체표체/수체표체조,분별진행통계분석.결과 78례공수체중CYP3A5*3*3 47례(60.3％),CYP3A5*1*328례(35.9％),CYP3A5*1*1 3례(3.8％).수체기인표체조비수체기인비표체조술후1、2、4、8주C0/D명현경저,차이유통계학의의(P＜0.05);공체기인표체조비공체기인비표체조수체술후1、2、4주G0/D명현경저,차이유통계학의의(P＜0.05);공체비표체/수체비표체조술후제1、2、4、8주G0/D현저고우공체/수체단일표체조급공체표체/수체표체조,차이유통계학의의(P＜0.05);공체/수체단일표체조여공체표체/수체표체조상비술후1、2、4、8주C0/D차이균무통계학의의(P＞0.05).결론 공수체CYP3A5기인다태성여간이식술후조기수체적타극막사용약제량급소체도적전혈곡치농도적개체화차이밀절상관,재인동활체간이식중수요동시고필공수체기인대수체술후타극막사약대동역학적영향,요체도상동적혈약농도,공체/수체기인형중지요기중일방함유CYP3A5*1등위기인,술후소수적타극막사제량취회상응증가.분석공수체CYP3A5기인다태성가이위간이식술후타극막사적개체화용약제공가고적삼고지표,지도최가적용약제량,제고약효병감소불량반응.
Objective To analyze CYP3A5 gene polymorphism of donor and recipient in children of living donor liver transplantation and examine the tacrolimus concentration/dose ratio after transplantation to provide reliable reference rationales for using tacrolimus after transplantation,optimize drug regimens and reduce adverse reactions.Methods Blood samples were collected from donor and living donor liver transplant in our treatment group.And the CYP3A5 genotypes were determined by polymerase chain reaction-sequence specific primer (PCR-SSP).The concentration/dose ratio was recorded after transplantation.According to the genotype of recipient,they were divided into recipient expression and non-expression groups; According to the genotype of donor,donor expression and non-expression groups; According to the genotype of donor and recipient,donor non-expression/ recipient non-expression,donor or recipient expression and donor expression/recipient expression.Results The CYP3A5 genotypes of 78 patients were composed of 47 CYP3A5 * 3 * 3 (60.3％),28 CYP3A5 * 1 * 3 (35.9％) and 3 CYP3A5 * 1 * 1 (3.8％).The C0/D of recipient expression group was significantly lower than that of recipient non-expression group at Week 1,2,4 and 8 post-transplantation.The C0/D of donor expression group was significantly lower than donor non-expression group at Week 1,2 and 4 post-transplantation.The G0/D of donor non-expression/recipient non-expression group was significantly lower than donor or recipient expression group at Week 1,2,4 and 8 post-transplantation.However,no significant difference existed between the G0/ D of donor or recipient expression group and the C0/D of the donor expression/recipient expression group at Week 1,2,4 and 8 post-transplantation.Conclusions CYP3A5 gene polymorphism is highly correlated with individual differences in the doses of tacrolimus and blood trough concentrations after transplantation.The CYP3A5 genotypes of donor and recipient have the same effect on G0/D ratio after living donor liver transplantation.
