[Beta1-adrenergic receptor (Arg389Gly) polymorphism and response to bisoprolol in patients with chronic heart failure].
OBJECTIVE
The purpose of this study was to investigate the relation between the Arg389Gly polymorphism of the beta(1)-AR gene and chronic heart failure (CHF) and to evaluate the effect of this polymorphism on clinical response to beta-adrenoceptor blockade (bisoprolol) in patients with CHF.


METHODS
One hundred and ten patients with stable CHF receiving basic therapy for heart failure were included. Before initiation and 3 months after the maximal tolerated dose of bisoprolol was reached, all indices (including BP, HR, LAD, LVEDD, LVESD, LVEF, BNP level, 6 min walk distance) were measured and compared with the Arg389Gly genotypes, which identified by PCR-restriction fragment length polymorphism analysis. We also determined the Arg389Gly genotypes in 100 healthy control subjects, and compared the distribution of Arg389Gly genotypes with that in CHF.


RESULTS
No difference was observed between the two groups in any of the three genotypes (CC, CG and GG). The prevalences of the three genotypes in normal subjects and patients with CHF were Arg389Arg 0.53 vs. 0.51, Arg389Gly 0.40 vs. 0.40, Gly38Gly 0.07 vs. 0.09, respectively. After 3 months of bisoprolol usage, a significant improvement in LVEF was observed in CC group, which increased from (36.7 +/- 8.63)% to (44.1 +/- 9.53)%, CG group, from (35.76 +/- 8.39)% to (42.90 +/- 9.41)%, but not GG group, from (36.00 +/- 5.66)% to (37.33 +/- 5.64)%. The improvement in BNP was also observed in CC [from (502.93 +/- 160.80) ng/L to (325.26 +/- 135.63) ng/L], CG [from (525.76 +/- 157.66) ng/L to (331.79 +/- 133.97) ng/L], but not GG [from (505.33 +/- 125.07) ng/L to (429.67 +/- 182.39) ng/L]. Arg389-homozygous patients showed a substantially greater improvement in LVEF and BNP, compared with Gly389-homozygous patients (all P < 0.01).


CONCLUSIONS
There was no difference in the prevalence of the three genotypes between healthy and CHF subjects. The Gly389 polymorphism of the beta(1)-AR gene was not associated with an increased risk of CHF. The Arg389 variant of the beta(1)-AR gene was associated with a greater response to bisoprolol than that of the Gly389 variant in patients with CHF.
Yu
Wen-ping
WP
Department of Cardiology, Tongji Hospital, Tongji University, Shanghai 200065, China.
Lou
Ming
M
Deng
Bing
B
Song
Hao-ming
HM
Wang
Hong-bao
HB
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017298:Bisoprolol / Q000627:therapeutic use*; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000188:drug therapy* / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D011110:Polymorphism, Genetic; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics*
D000319:Adrenergic beta-Antagonists; D018342:Receptors, Adrenergic, beta-1; D020097:Natriuretic Peptide, Brain; D017298:Bisoprolol