目的:研究肾移植患者中CYP3A4*1G和CYP3A5*3基因多态性对地尔硫?浓度/剂量比的影响。方法以47例肾移植患者为研究对象,用聚合酶链式反应-限制性内切片段长度多态性方法测定肾移植患者药物代谢酶基因型,用高效液相色谱法测定地尔硫?的血药浓度谷值,比较CYP3A4*1G和CYP3A5*3基因多态性对肾移植患者地尔硫?浓度/剂量比的影响。结果 CYP3 A4*1*1型14例(29.79%)、CYP3A4*1*1G型26例(55.32%),CYP3A4*1G*1G型7例(14.89%),G等位基因分布频率为57.45%,A等位基因分布频率为42.55%;CYP3A5*1*1型6例(12.77%), CYP3A5*1*3型21例(44.68%), CYP3A5*3*3型20例(42.55%),G等位基因分布频率为64.89%,A等位基因分布频率为35.11%。肾移植患者中CYP3A4*1G基因多态性对地尔硫?浓度/剂量比有显著影响,CYP3A4*1*1型受者比携带CYP3A4*1G等位基因肾移植患者的浓度/剂量比高1.52倍,差异有统计学意义( P<0.05);而CYP3A5*3基因多态性对浓度/剂量比影响较轻微,且差异无统计学意义。结论肾移植患者中CYP3A4*1G基因多态性对地尔硫?浓度/剂量比有显著影响。
Objective To investigate the impact of the CYP3A4*1G and CYP3 A5*3 polymorphisms on the concentration/dose ratios of dilti-azem in kidney transplant patients.Methods Forty -seven cases of kidney transplant recipients were recruited.CYP3A4 and CYP3A5 geno-types were determined by polymerase chain reaction -restriction fragment length polymorphism.Plasma trough concentration of diltiazem was meas-ured by HPLC.The effects of CYP3A4*1G and CYP3A5*3 gene poly-morphisms on the concentration/dose ratios of diltiazem were evaluated and compared.Results There were fourteen cases of CYP3A4*1*1 (29.79%) homozygous genotype , twenty six cases of CYP3A4*1*1G (55.32%) heterozygous genotype , and seven cases of CYP3A4*1G*1G (14.89%) homozygous genotype.Allele frequencies of CYP3A4*1 and *1G were 57.45%and 42.55%, respectively.There were six ca-ses with CYP3A5*1*1 (12.77%), twenty one cases with CYP3A5*1*3(44.68%), and twenty cases with CYP3A5*3*3(42.55%).Allele frequencies of CYP3A5*1 and *3 were 35.11%and 64.89%, respectively.CYP3A4*1G gene polymorphisms were significantly related to the concentration /dose of diltiazem in kidney transplant patients.The diltiazem blood trough concentration/dose in CYP3A4*1*1 recipients was 1.52 times higher than that in patients with CYP 3A4*1G allelic genes.There was significant difference in diltiazem blood trough concen-tration/dose ratios between recipients with CYP3A4*1*1 genotypes and CYP3A4*1G carriers(P<0.05).CYP3A5*3 gene polymorphisms had slight impacts on diltiazem blood trough concentration /dose ratios but no difference was found among the CYP3A5 genotypes.Conclusion The CYP3A4*1G gene polymorphism is closely related to the blood con-centration/dose ratios of diltiazem in kidney transplant patients.