Association of rs1042713 and rs1042714 polymorphisms of the ADRB2 gene with response to beta-blockers in the management of portal hypertension in patients with liver cirrhosis

Objective. To evaluate the association between polymorphic markers rs1042713 and rs1042714 of the β2-adrenergic receptor gene (ADRB2) and the response to oral propranolol in the management of portal hypertension (PH) in patients with liver cirrhosis (LC). Materials and Methods. A prospective cohort study included 47 unrelated patients with LC of various etiologies. Genotyping of rs1042713 and rs1042714 of the ADRB2 gene was performed using polymerase chain reaction followed by restriction fragment length polymorphism analysis (PCR–RFLP). Results. Heterozygous haplotype variants of the β2-adrenergic receptor gene were the most prevalent, observed in 51.06% of patients. Homozygous Gly16–Glu/Gln27 variants were identified in 36.17% of cases, whereas the Arg16–Gln27 haplotype was the least frequent (12.77%). Patients with the homozygous Gly16–Glu/Gln27 haplotype demonstrated the most favorable response to propranolol therapy (52.94%) compared with compound heterozygotes (20.83%) and homozygous Arg16–Gln27 carriers (0.00%). The likelihood of being a responder to propranolol therapy was more than threefold higher in carriers of the Gly16–Glu/Gln27 homozygous haplotype (p=0.01). In contrast, carriers of the Arg16–Gln27 homozygous haplotype had a 1.5-fold increased risk of non-response (p=0.0002). Conclusion. Interindividual variability in propranolol efficacy in patients with LC is associated with ADRB2 gene polymorphisms. The Arg16Gly substitution in the β2-adrenergic receptor is associated with an enhanced therapeutic response to propranolol.