To evaluate the impact of CYP2D6 gene polymorphic marker G1846A carriage on the hemodynamic effect of propranolol in patients with liver cirrhosis.
Material and methods
In a prospective study, we recruited 60 patients with liver cirrhosis and portal hypertenstion who were treated with propranolol at a daily dose of 30 mg for 14 days. The portal vein linear blood flow velocity was measured by ultrasonography. Genotyping of CYP2D6*4 was carried out by real-time polymerase chain reaction. The CYP2D6 activity was evaluated by the ratio of pinoline and its metabolite concentration in morning urine using high performance liquid chromatography with mass spectrometry.
At day 14, the mean portal vein linear blood flow velocity increased in 41 patients from 10.4 ± 3.9 cm/s up to 14.7 ± 4.3 cm/s (p<0.001). Twenty nine patients showed an increase in portal vein linear blood flow velocity by ≥20% from the initial value (p<0.001). The regression analysis showed a statistically significant effect of the CYP2D6 gene polymorphic marker G1846A carriage on the propranolol therapeutic effect (p<0.05). CYP2D6 activity did not depend on the severity of liver cirrhosis (p>0,05).
Our findings suggested an association between CYP2D6 gene polymorphic marker G1846A carriage and the hemodynamic effect of propranolol in patients with liver cirrhosis in the Russian population. Changes in the portal vein linear blood flow velocity were more prominent in carriers of the homozygous genotype CYP2D6 G/G1846 than in patients with the heterozygous genotype G/A1846.
Pharmacogenetics, liver cirrhosis, portal hypertension, CYP2D6, propranolol.