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Influence of beta‐2 adrenergic receptor gene polymorphism on the hemodynamic response to propranolol in patients with cirrhosis
Author(s) -
Turnes Juan,
HernándezGuerra Manuel,
Abraldes Juan G.,
Bellot Pau,
Oliva Rafael,
GarcíaPagán Juan Carlos,
Bosch Jaime
Publication year - 2006
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.21000
Subject(s) - medicine , propranolol , haplotype , endocrinology , hemodynamics , cirrhosis , genotype , allele , biology , gene , genetics
Abstract The beta‐2‐adrenergic receptor (β 2‐ ‐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 β 2 ‐AR may influence the hemodynamic response to propranolol in patients with cirrhosis. The β 2 ‐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 , β 2 ‐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. (H EPATOLOGY 2005;43:34–41.)