RESUMO
This study was performed to outline the different MDR-1 [Multi-Drug Resistance-1] genotypes in a sample of 37 Egyptian patients suffering from atrial fibrillation [AF] and/or congestive heart failure [CHF] and are using digoxin, to assess the role of MDR-1 genotypes polymorphism in affecting steady state serum digoxin therapeutic levels, and studying the consequences on patients' clinical outcome. Two venous blood samples were drawn from each patient; the 1[st] sample was taken, on admission, for DNA extraction and genotyping and the 2 [nd] was taken, 6 hours post dose after reaching steady state concentration, for serum digoxin assay. Serum digoxin. levels were assayed using EMIT 2000 analyzer, and MDR-1 genotyping was done using polymerase chain reaction-restriction fragment length polymorphism [PCR-RFLP] technique. Twenty patients [54.1%] showed serum digoxin levels within the therapeutic range, 12 patients [32.4%] showed serum digoxin levels under the minimum effective concentration [p< 0.9 ng/ml], while 5 patients [13.5%] showed serum digoxin levels over maximum safety concentration [> 2 ng/ml], with P value of 0.0001 among the three groups. MDR-1 genotyping revealed ten patients [27%] carrying the homozygous mutant TT genotype, 27 patients [73%] carrying the heterozygous mutant CT genotype, with no patient showing the wild CC genotype. Allelic distribution showed 42% for the wild type C allele while 58% for the homozygous mutant T allele. Patients carrying the homozygous mutant TT genotype showed significantly lower serum digoxin levels compared with those carrying the heterozygous mutant CT genotype [P value: 0.009]. Patients with significant improvement carried the CT genotype and had serum digoxin levels within the therapeutic range. In conclusion, patients with different MDR-1 genotypes had variations in their serum digoxin levels and identification of MDR-1 variations was found useful in predicting therapy outcome. We recommend further extensive work on large samples to study the important role of MDR-1 gene in affecting the disposition of different substrates, to be able for individualizing them according to the patients' genetic profile in order to improve drug therapy and reduce inter-patient variability