中国临床药理学杂志
中國臨床藥理學雜誌
중국림상약이학잡지
THE CHINESE JOURNAL OF CLINICAL PHARMACOLOGY
2014年
8期
667-670
,共4页
易鑫%汪江林%周亚男%陈清洁%成柯%明英姿%马颖%左笑丛
易鑫%汪江林%週亞男%陳清潔%成柯%明英姿%馬穎%左笑叢
역흠%왕강림%주아남%진청길%성가%명영자%마영%좌소총
地尔硫?%细胞色素P450 3 A4*1 G%细胞色素P450 3 A5*3%基因多态性%肾移植
地爾硫?%細胞色素P450 3 A4*1 G%細胞色素P450 3 A5*3%基因多態性%腎移植
지이류?%세포색소P450 3 A4*1 G%세포색소P450 3 A5*3%기인다태성%신이식
diltiazem%cytochrome P450 3A4*1G%cytochrome P450 3A5*3%gene polymorphisms%kidney transplant
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。
目的：研究腎移植患者中CYP3A4*1G和CYP3A5*3基因多態性對地爾硫?濃度/劑量比的影響。方法以47例腎移植患者為研究對象，用聚閤酶鏈式反應-限製性內切片段長度多態性方法測定腎移植患者藥物代謝酶基因型，用高效液相色譜法測定地爾硫?的血藥濃度穀值，比較CYP3A4*1G和CYP3A5*3基因多態性對腎移植患者地爾硫?濃度/劑量比的影響。結果 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等位基因分佈頻率為57.45％，A等位基因分佈頻率為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等位基因分佈頻率為64.89％，A等位基因分佈頻率為35.11％。腎移植患者中CYP3A4*1G基因多態性對地爾硫?濃度/劑量比有顯著影響，CYP3A4*1*1型受者比攜帶CYP3A4*1G等位基因腎移植患者的濃度/劑量比高1.52倍，差異有統計學意義（ P＜0.05）；而CYP3A5*3基因多態性對濃度/劑量比影響較輕微，且差異無統計學意義。結論腎移植患者中CYP3A4*1G基因多態性對地爾硫?濃度/劑量比有顯著影響。
목적：연구신이식환자중CYP3A4*1G화CYP3A5*3기인다태성대지이류?농도/제량비적영향。방법이47례신이식환자위연구대상，용취합매련식반응-한제성내절편단장도다태성방법측정신이식환자약물대사매기인형，용고효액상색보법측정지이류?적혈약농도곡치，비교CYP3A4*1G화CYP3A5*3기인다태성대신이식환자지이류?농도/제량비적영향。결과 CYP3 A4*1*1형14례（29.79％）、CYP3A4*1*1G형26례（55.32％），CYP3A4*1G*1G형7례（14.89％），G등위기인분포빈솔위57.45％，A등위기인분포빈솔위42.55％；CYP3A5*1*1형6례（12.77％）， CYP3A5*1*3형21례（44.68％）， CYP3A5*3*3형20례（42.55％），G등위기인분포빈솔위64.89％，A등위기인분포빈솔위35.11％。신이식환자중CYP3A4*1G기인다태성대지이류?농도/제량비유현저영향，CYP3A4*1*1형수자비휴대CYP3A4*1G등위기인신이식환자적농도/제량비고1.52배，차이유통계학의의（ P＜0.05）；이CYP3A5*3기인다태성대농도/제량비영향교경미，차차이무통계학의의。결론신이식환자중CYP3A4*1G기인다태성대지이류?농도/제량비유현저영향。
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.
