Impact of CYP2D6 Polymorphisms on Propranolol Response in Children with Portal Hypertension

Abstract

ropranolol is a synthetic non-selective beta-adrenergic receptor blocking agent which is used in primary and secondary prevention of variceal bleeding in both patients with cirrhosis and non cirrhotic portal hypertension through both β-1 and β-2 blockade (Miñano and Garcia-Tsao, 2010; Steenen et al., 2015). Propranolol dose should be adjusted to obtain a 20%–25% reduction in heart rate (Lebrec et al., 2005). Propranolol act on the autonomic nervous system, and HRV can be used to explore its influence on sympathetic and parasympathetic activity (Ernst, 2017). CYP2D6 is the rate-limiting enzyme for the metabolism of Propranolol and it is involved in phase I metabolism of Propranolol. CYP2D6 is highly polymorphic and represents one of the most difficult enzymes to genotype (Ingelman-Sundberg et al., 1999). In current prospective study, we investigated whether the CYP2D6 genotypes and metabolizer phenotypes affect Propranolol response (decrease HR 25%, Doppler findings, endoscopic findings and heart rate variability data) because the effect of propranolol is not consistent in children.