[Genetic aspects of individual sensitivity to betaxolol in patients with arterial hypertension].
Association of polymorphism of b1-adrenoreceptors gene and cytochrome 2D6 gene with efficacy of b-adrenoblocker betaxolol was studied in 81 patients with I and II degree arterial hypertension. Betaxolol (10-20 mg/day) was given for 4 weeks, its efficacy was assessed by office blood pressure (BP) measurements, 24-hour BP and ECG monitoring and standard exercise test. At the end of the study significant lowering of systolic and diastolic BP was noted by 11,8 +/- 2,47 (p=0,001) and 7,8 +/- 1,68 mm Hg (p=0,001), respectively. Heart rate (HR) at rest lowered by 19,8 +/- 1,96 beats/min (p=0,0001). At analysis of individual reaction of patients to treatment with betaxolol it turned out that decrease of BP and HR was variable, but their distribution in the group did not differ significantly from normal. Hypotensive activity and influence on HR were confirmed by results of all instrumental investigations. No significant differences were revealed in dynamics of systolic and diastolic BP both at rest and at effort between patients with different genotypes of polymorphic marker Gly389Arg of ADRB1 gene. Compared with carriers of genotype Ser/Ser carriers of genotype Ser/Pro of polymorphic marker Pro34Ser of Cyp2D6 gene had significantly more pronounced decrease of HR at the background of treatment with betaxolol: - 32,6 +/- 4,77 and - 18,4 +/- 2,01 beats/min (p=0,023) at rest and - 30,1 +/- 3,05 and - 24,0 +/- 2,59 beats/min (p=0,043) at maximal exercise, respectively. These patients had also more pronounced lowering of diastolic BP at maximal work load and more pronounced increase of exercise duration at the background of treatment. Thus efficacy of betaxolol in patients with hypertension was associated solely with genotype of polymorphic marker Ser34Pro of CYP2D6 gene. In patients having in genotype Pro allele of polymorphic marker Pro34Ser of CYP2D6 gene therapy with betaxolol is more effective, than in homozygote carriers of Ser allele. This can be related to low rate of metabolism of the preparation in these patients.
Minushkina
L O
LO
Presidential Medical Center of Russia, Moscow, Russia.
Zateĭshchikova
A A
AA
Zateĭshchikov
D A
DA
Mankhaeva
B B
BB
Savel'eva
E G
EG
Kochkina
M S
MS
Brovkin
A V
AV
Nikitin
A G
AG
Nosikov
V V
VV
Sidorenko
B A
BA
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000483:Alleles; D015784:Betaxolol / Q000627:therapeutic use*; D001794:Blood Pressure; D019389:Cytochrome P-450 CYP2D6 / Q000097:blood / Q000235:genetics*; D004247:DNA / Q000235:genetics*; D015716:Electrocardiography, Ambulatory; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000187:drug effects*; D018342:Receptors, Adrenergic, beta-1 / Q000097:blood / Q000235:genetics*; D012307:Risk Factors; D016896:Treatment Outcome
D000319:Adrenergic beta-Antagonists; D018342:Receptors, Adrenergic, beta-1; D004247:DNA; D019389:Cytochrome P-450 CYP2D6; D015784:Betaxolol