Influence of beta-2 adrenergic receptor gene polymorphism on the hemodynamic response to propranolol in patients with cirrhosis

Authors

  • Juan Turnes,

    1. Hepatic Hemodynamic Laboratory, Liver Unit, Institut de Malalties Digestives i Metaboliques, Hospital Clínic, IDIBAPS, Barcelona, Spain
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  • Manuel Hernández-Guerra,

    1. Hepatic Hemodynamic Laboratory, Liver Unit, Institut de Malalties Digestives i Metaboliques, Hospital Clínic, IDIBAPS, Barcelona, Spain
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  • Juan G. Abraldes,

    1. Hepatic Hemodynamic Laboratory, Liver Unit, Institut de Malalties Digestives i Metaboliques, Hospital Clínic, IDIBAPS, Barcelona, Spain
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  • Pau Bellot,

    1. Hepatic Hemodynamic Laboratory, Liver Unit, Institut de Malalties Digestives i Metaboliques, Hospital Clínic, IDIBAPS, Barcelona, Spain
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  • Rafael Oliva,

    1. Human Genetics Laboratory, Hospital Clínic i Facultat de Medicina, Universitat de Barcelona, IDIBAPS, Barcelona. Spain
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  • Juan Carlos García-Pagán,

    1. Hepatic Hemodynamic Laboratory, Liver Unit, Institut de Malalties Digestives i Metaboliques, Hospital Clínic, IDIBAPS, Barcelona, Spain
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  • Jaime Bosch

    Corresponding author
    1. Hepatic Hemodynamic Laboratory, Liver Unit, Institut de Malalties Digestives i Metaboliques, Hospital Clínic, IDIBAPS, Barcelona, Spain
    • Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Villarroel 170, Barcelona 08036, Spain
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    • fax: (34) 93 22 79 348


  • Potential conflict of interest: Nothing to report.

Abstract

The beta-2-adrenergic receptor (β2--AR) has several single-nucleotide polymorphisms. These influence the functional response to adrenergic stimulation; genotypes homozygous for Gly16-Glu27 or Gly16-Gln27 alleles (Gly16-Glu/Gln27 haplotypes) are associated with enhanced response, whereas genotypes homozygous for Arg16-Gln27 alleles (Arg16-Gln27) show a decreased response. We hypothesized that gene polymorphisms at the β2-AR may influence the hemodynamic response to propranolol in patients with cirrhosis. The β2-AR gene polymorphisms were determined by direct sequencing of the polymerase chain reaction (PCR) products in 48 patients with cirrhosis. All patients also had hepatic and systemic hemodynamic studies before and after propranolol administration. Prevalence of Gly16-Glu/Gln27 haplotypes was 29.1%, Arg16-Gln27 haplotype was 16.7%, and 54.2% were compound heterozygotes. Patients with cirrhosis with Gly16-Glu/Gln27 haplotypes had a greater decrease in heart rate, cardiac index, and hepatic blood flow after propranolol administration than those with Arg16-Gln27 haplotype. However, the HVPG response to propranolol was similar in both groups, whereas estimated hepatic sinusoidal resistance increased significantly in Gly16-Glu/Gln27 haplotypes but not in Arg16-Gln27 (+27.1 ± 17.8% vs -17.9 ± 13.9%, P = .042), suggesting that unopposed vasoconstrictive activity at the intrahepatic circulation hinders the fall in HVPG despite enhanced hemodynamic response to propranolol in Gly16-Glu/Gln27 haplotypes. In conclusion, β2-AR gene polymorphisms influence the response to beta-blockade. However, HVPG reduction cannot be predicted from polymorphism analysis. Patients with the Gly16-Glu/Gln27 haplotypes may benefit from the association of hepatic vasodilators to propranolol therapy. (HEPATOLOGY 2005;43:34–41.)

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