β₁-adrenergic Receptor (Arg389Gly) Polymorphism And Response To Bisoprolol In Patients With Chronic Heart Failure

Objective:Mutation scanning of theβ₁-adrenoceptor gene has identified apolymorphism, Arg389Gly, that markedly affects G-protein coupling of the receptorand resulting cAMP production. Previous studies have suggested a potentialpharmacogenic interaction betweenβ-blocker therapy and theβ₁-adrenergic receptorpolymorphism. Our objectives were to investigate the relation between theArg389Gly polymorphsm of theβ₁-AR gene and chronic heart failure and alsoinvestigated the effect of this functionally active polymorphism on clinical responsetoβ-adrenoceptor blockade (bisoprolol) in patients with chronic heart failure.Methods:We studied 105 patients with stable CHF who were receiving basic therapyfor heart failure.Before initiation of bisoprolol and 3 months after the maximaltolerated dose was reached,all indices (including—BP,HR, LAD,LVEDd,LVESd,LVEF,BNP level, 6rain walk distance,) were measured and compared with theArg389Gly genotype, ascertained by PCP／restriction fragment length polymorphism.We also measured the Arg389Gly genotype in 100 healthy control subjects. andcompare the Arg389Gly genotype with CHF.Results: No differences was observed in the distribution of any of the three genotypesin patients with CHF and normal subjects. The prevalence of the three genotypes innormal subjects and CHF was ArgArg (53%versus51%, ArgGly40%versus 40%,GlyGly7%versus 9%). After 3 months of Bisoprolol usage,a significantimprovement in LVEF was observed in CC(from36.7±8.63 to 44.1±9.53),CG(from35.76±8.39 to 42.90±9.41),but not GG(from 36.00±5.66 to 37.33±5.64);improvement in BNP was also observed in CC(from502.93±160.80to325.6±135.63),CG(from 525.76±157.66 to 331.79±133.97),but not GG(from505.33±125.07to 429.67±182.39); Arg389 homozygous patients showed asubstantially greater improvement in LVEF and BNP,compared with Gly389-homozygous patients(p=0.010, p=0.000),but like as Arg389Gly (p〉0.05). Conclusions:There were no difference in the prevalence of the the three genotypesbetween healthy subjects and CHF, the Gly389 polymorphsm of theβ1-AR gene arenot associated with an increased risk of CHF;The Arg389 variant of theβ1-AR genewas associated with a greater response to bisoprolol than that of the Gly389 variant inpatients with CHF.