篇名: ABCB1基因多态性与肾移植患者围手术期服用他克莫司相关不良反应的相关性
摘要: 目的:探讨腺苷三磷酸(ATP)结合盒转运体B1(ABCB1)基因多态性与肾移植患者围手术期服用他克莫司相关不良反应的相关性。方法:选取2014年11月-2018年3月于我院行肾移植术且术后服用他克莫司的患者170例,检测其ABCB1 C1236T(rs1128503)、ABCB1 G2677T/A(rs2032582)和ABCB1 C3435T(rs1045642)基因型。采用χ2检验比较不同基因型患者间他克莫司相关不良反应的发生率,相关不良反应包括消化道反应、肺部感染、肾功能异常、肝功能异常、血糖升高、血脂升高、白细胞降低。采用Logistic回归模型进行单位点危险度分析。应用PHASE软件分析患者上述基因的主要单倍型,并分析其主要单倍型与他克莫司相关不良反应的相关性。结果:170例患者中,ABCB1 C1236T(rs1128503)检测结果显示CC型21例(占12.3%)、CT型78例(占45.9%)、TT型71例(占41.8%);ABCB1 G2677T/A(rs2032582)检测结果显示GG型25例(占14.7%)、GA+GT型95例(占55.9%)、AA+AT+TT型50例(占29.4%);ABCB1 C3435T(rs1045642)检测结果显示CC型57例(占33.5%)、CT型82例(占48.2%)、TT型31例(占18.3%)。不同ABCB1基因型患者间消化道反应、肺部感染、肾功能异常、血糖升高、血脂升高、白细胞降低的发生率差异均无统计学意义(P>0.05),但ABCB1 C1236T(rs1128503)及ABCB1 C3435T(rs1045642)不同基因型患者间肝功能异常的发生率差异有统计学意义(P<0.05),ABCB1 G2677T/A(rs2032582)不同基因型患者间肝功能异常的发生率差异虽无统计学意义(P=0.069),但P<0.1。Logistic回归分析显示,ABCB1 C1236T(rs1128503)CC型[OR=4.959,95%CI(1.700,14.468),P=0.003]、ABCB1 G2677T/A(rs2032582)GG型[OR=3.500,95%CI(1.164,10.524),P=0.026]以及ABCB1 C3435T(rs1045642)CC型[OR=3.033,95%CI(1.012,9.095),P=0.048]均为他克莫司致相关肝功能异常的风险因子。ABCB1 CGC单倍型为主要单倍型,其携带与否与他克莫司相关肝功能异常的发生率差异存在统计学意义(P=0.002),且是他克莫司相关肝功能异常的风险因子[OR=3.173,95%CI(1.512,6.656),P=0.002]。结论:携带ABCB1 CGC单倍型的肾移植患者围手术期服用他克莫司出现肝功能异常的可能性较大。
ABSTRACT: OBJECTIVE: To investigate the relationship between ATP-binding cassette subfamily B member 1 (ABCB1) polymorphism and tacrolimus-related adverse drug reactions in renal transplant patients during perioperative period. METHODS: Totally 170 patients who underwent renal transplantation from Nov. 2014 to Mar. 2018 in our hospital as well as were tested for their ABCB1 C1236T (rs1128503), ABCB1 G2677T/A (rs2032582) and ABCB1 C3435T (rs1045642) genotype were selected in this study. χ2 test was used to compare the incidence of tacrolimus-related ADR among patients with different genotypes. The related adverse reactions included digestive tract reaction, pulmonary infection, renal dysfunction, abnormal liver function, elevated blood sugar, elevated blood lipid and decreased white blood cells. Logistic regression model was used to analyze the unit point risk. The main haplotypes of the above genes were analyzed by PHASE software, and their correlation with tacrolimus-induced ADR was analyzed. RESULTS: Among 170 patients, 21 cases (12.3%) of CC type, 78 cases (45.9%) of CT type and 71 cases (41.8%) of TT type were detected by ABCB1 C1236T (rs1128503). ABCB1 G2677T/A (rs2032582) test showed that 25 cases (14.7%) were GG type, 95 cases (55.9%) were GA+GT type and 50 cases (29.4%) were AA+AT+TT type. ABCB1 C3435T (rs1045642) test showed that 57 cases (33.5%) were CC type, 82 cases (48.2%) were CT type and 31 cases (18.3%) were TT type. There was no significant difference in the incidence of digestive tract reaction, pulmonary infection, renal dysfunction, elevated blood sugar, elevated blood lipid and decreased white blood cells among patients with different ABCB1 genotypes (P>0.05). However, there was significant difference in the incidence of abnormal liver function between ABCB1 C1236T (rs1128503) and ABCB1 C3435T (rs1045642) genotypes (P<0.05). There was no significant difference in the incidence of abnormal liver function among ABCB1 G2677T/A (rs2032582) genotypes (P=0.069), but P was lower than 0.1. Logistic regression analysis showed that ABCB1 C1236T (rs1128503) CC genotype [OR=4.959, 95%CI (1.700, 14.468), P=0.003], ABCB1 G2677T/A (rs2032582) GG genotype [OR=3.500, 95%CI (1.164, 10.524), P=0.026] and ABCB1 C3435T (rs1045642) CC genotype [OR=3.033, 95%CI (1.012, 9.095), P=0.048] were risk factors for tacrolimus-related abnormal liver function. ABCB1 CGC haplotype was the main haplotype. There was significant difference in the incidence of abnormal liver function caused by tacrolimus between ABCB1 CGC haplotype and non-ABCB1 CGC haplotype (P=0.002), and it was also a risk factor for tacrolimus-related liver dysfunction [OR=3.173, 95%CI(1.512, 6.656), P=0.002]. CONCLUSIONS: The abnormal liver function of ABCB1 CGC haplotype kidney transplantation patients is more likely to occur when tacrolimus is administered during the perioperative period.
期刊: 2019年第30卷第19期
作者: 谢培华,蔡宜朋,陈泉金,宋洪涛
AUTHORS: XIE Peihua,CAI Yipeng,CHEN Quanjin,SONG Hongtao
关键字: ABCB1基因多态性;他克莫司;不良反应;肝功能异常;肾移植
KEYWORDS: ABCB1 gene polymorphism; Tacrolimus; Adverse drug reactions; Abnormal liver function; Renal transplant
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