CYP2D6 gene polymorphism effect on central hemodynamic parameters in patients with portal hypertension taking propranolol

Introduction. Despite the huge number of modern recommendations for the treatment of patients with liver cirrhosis, there is still no clear scheme for prescribing non-selective beta-blockers.

Aim. To evaluate effect of polymorphic markers CYP2D6*3, CYP2D6*4, CYP2D6*10 and CYP2D6*41 carriage on central hemodynamics in patients with liver cirrhosis during propranolol therapy.

Materials and methods. The study included 60 patients with liver cirrhosis who received propranolol therapy at a daily dose of 30 mg for 14 days. The efficacy of treatment was assessed by dynamic measurement of heart rate, systolic and diastolic blood pressure, ultrasonography measuring the  linear blood flow velocity of  portal vein. Genotyping of  CYP2D6*3, CYP2D6*4, CYP2D6*10 and CYP2D6*41 was carried out by real-time polymerase chain reaction.

Results and discussion. Positive hemodynamics in the form of a decrease in systolic and diastolic blood pressure, an increase in the average linear blood flow velocity of the portal vein compared with the baseline was observed in 41 patients. SBP and DBP decreased by 8.05 mm Hg (p = 0.006) and 4.51 mm Hg (p = 0.037), respectively. Our regression analysis revealed the presence of  a statistically significant effect of  carriage of  the CYP2D6*4  polymorphic marker on the  therapeutic effect of  propranolol (p < 0.05). No statistically significant effect of polymorphic markers CYP2D6*3, CYP2D6*10 and CYP2D6*41 was found (p > 0.05).

Conclusion. The influence of carriage of the polymorphic marker CYP2D6*4 on the hemodynamic effect of propranolol in patients with liver cirrhosis of the Russian population was determined. In carriers of the homozygous GG genotype for CYP2D6*4, there is a more pronounced positive trend in lowering blood pressure during propranolol therapy, in contrast to patients with a heterozygous GA genotype. Based on the results of the study, the existing algorithm for personalizing the treatment of patients with liver cirrhosis with non-selective β-blockers using CYP2D6 genotyping was modernized. 

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