Effect of CYP3A4*1G/3A5*3 gene polymorphism on concentration/dose ratios of diltiazem in kidney transplant patients
- VernacularTitle:CYP 3A4*1G和3A5*3基因多态性对肾移植患者地尔硫浓度／剂量比的影响
- Author:
YI-Xin
1
;
Jiang-Lin WANG
;
Ya-Nan ZHOU
;
Qing-Jie CHEN
;
Ke CHENG
;
Ying-Zi MING
;
Ying MA
;
Xiao-Cong ZUO
Author Information
1. 湘潭市中心医院 科教科
- Keywords:
diltiazem;
cytochrome P450 3A4*1G;
cytochrome P450 3A5*3;
gene polymorphisms;
kidney transplant
- From:
The Chinese Journal of Clinical Pharmacology
2014;(8):667-670
- CountryChina
- Language:Chinese
-
Abstract:
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.
