Genetic polymorphisms of beta1 adrenergic receptor and their influence on the cardiovascular responses to metoprolol in a South Indian population.
OBJECTIVE
Beta-blockers show interindividual and interethnic variability in their response. Such variability might be due to the polymorphic variations in the beta1 adrenergic receptor genes viz, Ser49Gly and Arg389Gly. The study evaluated the influence of Ser49Gly and Arg389Gly polymorphisms on the cardiovascular responses to metoprolol in a South Indian population.


METHODS
Forty-one genetically prescreened healthy male volunteers participated in the study. They were divided on the basis of genotype of each polymorphism: Ser49Ser, Ser49Gly, and Gly49Gly and Arg389Arg, Arg389Gly, and Gly389Gly. They were also grouped into combination genotypes viz, S49S R389R, S49G R389R, G49G R389R, S49S R389G, S49S G389G, and S49G R389G. They were subjected to treadmill exercise testing, and cardiovascular parameters were measured before and after metoprolol administration. Metoprolol concentration was determined by reversed phase high-performance liquid chromatography method.


RESULTS
The diastolic blood pressure (DBP) was significantly lower in S49S/G389G group when compared to S49S/A389A group. The cardiac parameters were significantly increased in all the genotype groups during treadmill exercise test done for a period of 9 minutes. During predrug treadmill exercise at the end of third and sixth minute, Gly49Gly showed a higher increase in heart rate and volume of oxygen consumption compared to Ser49Ser. Same group showed a higher increase of volume of oxygen consumption at the end of ninth minute of exercise compared to the Ser49Ser. Systolic and diastolic blood pressures were not different between Ser49Gly polymorphisms. However, there was no statistical difference between the genotype groups of both polymorphisms at any stage of post-drug treadmill exercise. The analysis of combination of genotypes showed no significant difference during predrug and postdrug exercise testing.


CONCLUSIONS
The increase in cardiac responses to treadmill test was influenced by Ser49Gly polymorphism. Nevertheless, the above polymorphisms did not alter the beta-blocker response during treadmill exercise in South Indian population.
Mahesh Kumar
Koratagere Nagaraju
KN
Department of Pharmacology, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry-605006, India.
Ramu
Periasamy
P
Rajan
Subramanian
S
Shewade
Deepak Gopal
DG
Balachander
Jayaraman
J
Adithan
Chandrasekaran
C
D000293:Adolescent; D058671:Adrenergic beta-1 Receptor Antagonists; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000328:Adult; D005080:Exercise Test; D005787:Gene Frequency; D006439:Hemodynamics / Q000187:drug effects / Q000235:genetics; D006801:Humans; D007194:India; D008297:Male; D008790:Metoprolol / Q000494:pharmacology*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics*; D055815:Young Adult
D058671:Adrenergic beta-1 Receptor Antagonists; D000319:Adrenergic beta-Antagonists; D018342:Receptors, Adrenergic, beta-1; D008790:Metoprolol