Influence of CYP2D6 and β2-adrenergic receptor gene polymorphisms on the hemodynamic response to propranolol in Chinese Han patients with cirrhosis

Abstract

Background and aim: Propranolol is widely used to prevent gastroesophageal variceal bleeding; however, some patients could not benefit from propranolol. This study is to evaluate the relationship between CYP2D6 and β2-adrenergic receptor (β2-AR) gene polymorphisms and the hemodynamic response to propranolol in Chinese Han patients.

Methods: The clinical data of patients with gastroesophageal varices undergoing hepatic venous pressure gradient (HVPG) measurement before and 7 days after oral propranolol administration in our department were collected. Four single nucleotide polymorphisms of CYP2D6 and β2-AR genes were detected. The relationship was identified by logistic regression model.

Results: Thirty patients were involved in the analysis. Sixty milligram propranolol twice each day was well tolerated by all the patients. The initial and secondary average of HVPG was 17.4 ± 5.8 mmHg vs. 13.2 ± 4.8 mmHg, respectively (t = 5.726, P < 0.001). Twenty patients responded to propranolol. The mean reduction value of HVPG was 6.6 ± 3.6 mmHg (range from 3 to 19). Genotype analysis showed: 20 homozygotes for C/C188 and 10 for heterozygous C/T188, 8 homozygotes for G/G4268 and 22 heterozygotes for G/C4268, 14 homozygotes for Gly16 and 10 heterozygotes, and 6 homozygotes for Arg16, 27 homozygotes for Gln27 and 3 heterozygotes. The multivariate logistic regression analysis indicated that CYP2D6 (188C>T) genotype was an independent predicting factor for HVPG response to propranolol (P = 0.033).

Conclusions: CYP2D6 (188C>T) gene polymorphisms influence the hemodynamic response to propranolol in this population of Chinese Han patients with gastroesophageal varices. However, HVPG response cannot be completely predicted from CYP2D6 and β2-AR gene polymorphisms.

Keywords: CYP2D6; HVPG response; liver cirrhosis; propranolol; β2-AR.