Background: Digoxin is a substrate of P-glycoprotein (P-gp) and organic anion transporting polypeptide transporters that are encoded by ABCB1 and SLCO1B3 genes. Genetic polymorphisms in both genes may explain inter-individual variability of serum digoxin concentration (SDC). This study evaluates the possible effect of the most common ABCB1 and SLCO1B3 polymorphisms on SDC after a single oral dose of digoxin in Tunisian atrial fibrillation (AF) patients. Methods:ABCB1 and SLCO1B3 genotypes were analyzed in 102 patients with AF who received digoxin (0.5 mg) without (group I, n = 58) or with the co-administration of P-gp inhibitors (group II, n = 44). SDCs were determined at 6 h following the oral dose. Results: SDCs levels were significantly higher in patients who were co-administered P-gp inhibitors. No influence was noted in ABCB1 and SLCO1B3 polymorphisms on SDC in group I patients. However, SDCs values were significantly different among ABCB1 single nucleotide polymorphisms (SNPs) genotypes of 2677G>T/A (TT, GG>GT, p < 0.05) and 3435C>T (TT, CC>CT, p < 0.05) only in group II with no effect of 1236C>T and SLCO1B3 SNPs. Conclusion: Results suggest that P-gp inhibitors and ABCB1 gene polymorphisms may affect digoxin pharmacokinetics.
The Renin Angiotensin Aldosteron System (RAAS) is one of the major systems involved in the pathophysiology of heart failure. In this study we investigate the association between the renin angiotensin aldosteron system genes polymorphisms and acute heart failure (AHF) and we evaluate the role of serum ACE activity.
Methods:We included 300 patients over 20 years old admitted to the Emergency Department for acute dyspnea. According to the clinical findings and results of the B-type natriuretic peptide (BNP level), patients were divided into two groups: heart failure (HF) and non-heart failure (non-HF) groups. Genotyping was done by PCR-RFLP. The level of serum ACE activity was determined by spectrophotometric method using hippuryl histidyl leucine. We found the diagnosis of AHF in 50% of the population.
Results:No association between the renin polymorphism and AHF, but we found an association between ACE ID and CYP11B2 polymorphisms and heart failure. Level of serum ACE activity is significantly higher in the group of AHF.
Conclusion:We can conclude that blood ACE activity, ACE ID and CYP11B2 can be a marker of acute heart failure.
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