The Influence Of MDR1 And CYP3A Genetic Polymorphisms On Serum Digoxin Concentration

Objective:to determine the frequencies of MDR1C3435T, CYP3A4*18B and CYP3A5*3 in Chinese Han patients with chronic heart failure and to observe the impact of MDR1C3435T, CYP3A4*18B and CYP3A5*3 genetic polymorphism on serum digoxin concentration. This study provides an important theoretical evidence for the gene-directed rationalization and individualization of medication for digoxin.Methods:A group of 111 unrelated Chinese Han patients with chronic heart failure were recruited after them taken therapeutic drug monitoring (TDM). Demographic data, blood, liver and kidney function data and drug combination data were retrospectively collected. In addition, genotyping of MDR1C3435T, CYP3A4*18B and CYP3A5*3 alleles were conducted by PCR-RFLP method. We investigated above data and analyzed the effect of MDR1C3435T, CYP3A4*18B and CYP3A5*3 genetic polymorphism on serum digoxin concentration.Results:(1) The dosage of digoxin for 111 Chinese Han patients is 0.125mg, Qd; and the mean of serum digoxin concentration is 1.06±0.72ng/mL; (2)The frequencies of MDR1C3435T, CYP3A4*18B and CYP3A5*3 in Chinese Han patients of Guizhou were 39.60％,30.60% and 66.70%, respectively. The allelic frequency was consistent with Hardy-Weinberg equilibrium; (3)The serum digoxin concentration in MDR1CC3435 and MDR1TT3435 groups showed a significant difference, with a mean TDM value 0.89+0.55 ng/mL versus 1.37±0.95 ng/mL (P<0.05); (4)There were no statistical difference on the serum digoxin concentration with CYP3A4*18B or CYP3A5*3 genetic polymorphism (P>0.05).Conclusions:(1) The effect of MDR1C3435Tgenetic polymorphism increased the serum digoxin concentration; (2) CYP3A4*18B or CYP3A5*3 genetic polymorphism may have no significant effect on the serum digoxin concentration.