Frequency of genetic polymorphism for adrenergic receptor beta and cytochrome p450 2D6 enzyme, and effects on tolerability of beta-blocker therapy in heart failure with reduced ejection fraction patients: The Beta GenTURK study.
OBJECTIVE
The present objective was to determine frequency of Arginine389Glycine (Arg389Gly) and Cytochrome p450 2D6*10 (Cyp2D6*10) polymorphism in cases of heart failure-reduced ejection fraction (HFREF), and to evaluate the influence of the polymorphisms in response to beta-blocker (BB) therapy.


METHODS
A total of 206 HFREF patients and 90 healthy controls were prospectively enrolled. Genotypes for Arg389Gly and Cyp2D6*10 polymorphisms of the healthy controls and 162 of the 206 heart failure (HF) patients were measured, identified by polymerase-chain-reaction- and restriction-fragment-length-polymorphism analysis. HFREF patients and healthy controls were compared regarding Arg389Gly polymorphism. The HFREF patients were separated into 2 subgroups based on achievement of maximal target dose (MTD) of BB.


RESULTS
When comparing frequency of genotype distribution for Arg389Gly polymorphism in HFREF patients to the healthy controls, a statistically significant association was observed with CC genotype and Glisin-Glisin (GG) genotype (p<0.001, odds ratio [OR]=16, confidence interval [CI]: 3.8-67.9 and p<0.001, OR=0.3, CI: 0.2-0.6). Frequency of genotypes for Arg389Gly and Cyp2D6*10 polymorphism were similar in patients who could or could not achieve BB MTD (p=0.13 and p=0.60, respectively).


CONCLUSIONS
The frequency of Arg389Gly polymorphism in patients with HFREF in the present Turkish population differed from that of the healthy controls. However, neither Arg389Gly polymorphism nor Cyp2D6*10 polymorphism was associated with dose tolerability of BB therapy.
Department of Cardiology, Ege University Faculty of Medicine, İzmir, Turkey.
Mehdi
M
Zoghi
Department of Cardiology, Cumhuriyet University Faculty of Medicine, Sivas, Turkey. drhakkikaya84@gmail.com.
Hakkı
H
Kaya
Department of Cardiology, Osmangazi University Faculty of Medicine, Eskişehir, Turkey.
Yüksel
Y
Çavuşoğlu
Department of Cardiology, Atatürk University Faculty of Medicine, Erzurum, Turkey.
Enbiya
E
Aksakal
Department of Cardiology, Çukurova University Faculty of Medicine, Adana, Turkey.
Şerafettin
Ş
Demir
Department of Cardiology, Çukurova University Faculty of Medicine, Balcalı Hospital, Adana, Turkey.
Ceyhun
C
Yücel
Department of Cardiology, İstanbul University Faculty of Medicine, İstanbul, Turkey.
Haşim
H
Mutlu
Department of Cardiology, Atatürk Training and Research Hospital, İzmir, Turkey.
Oktay
O
Ergene
Department of Cardiology, Cumhuriyet University Faculty of Medicine, Sivas, Turkey.
Mehmet Birhan
MB
Yılmaz
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000368:Aged; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics*; D006333:Heart Failure / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011446:Prospective Studies; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics*; D013318:Stroke Volume; D014421:Turkey / Q000453:epidemiology
C547787:ADRB1 protein, human; D000319:Adrenergic beta-Antagonists; D018342:Receptors, Adrenergic, beta-1; D019389:Cytochrome P-450 CYP2D6