CYP 2D6*4 polymorphism and interindividual response variation to metoprolol in stage 1 hypertensive patients: no association in a rural Indian population?

JESTIN, Chelliah; AYYAPPADHAS, Rajagopal; DHANALEKSHMI, Unnikrishnan

CYP 2D6*4 polymorphism and interindividual response variation to metoprolol in stage 1 hypertensive patients: no association in a rural Indian population?

Rajagopal AYYAPPADHAS, (AIMST University, Kuala Lumpur, Malaysia)

Unnikrishnan DHANALEKSHMI, (Institute of Pharmacology, Madras Medical College, Chennai, India)

Chelliah JESTIN (International Medical University, Kuala Lumpur, Malaysia)

Turkish Journal of Medical Sciences

1 0

Yıl: 2015 Cilt: 45 Sayı: 2 Sayfa Aralığı: 352 - 357 Metin Dili: İngilizce İndeks Tarihi: 29-07-2022

CYP 2D6*4 polymorphism and interindividual response variation to metoprolol in stage 1 hypertensive patients: no association in a rural Indian population?

Öz:

Background/aim: Genetic polymorphism of CYP2D6 shows diverse pharmacokinetic and pharmacodynamic variation. Terefore, thepresent work was designed to study the variation in therapeutic responses to metoprolol (MP) in stage 1 hypertensive patients and alsoaims to verify the association of CYP2D6*4 polymorphism and response variation in an Indian population for the frst time.Materials and methods: Clinically, a total of 119 hypertensive patients and 116 healthy individuals as controls were included. Patientswere treated with MP extended release 25 mg tablets once daily for 2 weeks. Reduction in systolic blood pressure, diastolic bloodpressure, and pulse rate were recorded before and afer the treatment. For genotyping, genotypes of 89 hypertensive patients and 71healthy controls were investigated for CYP2D6*4 polymorphism.Results: Based on reduction in systolic blood pressure, 26% of the patients did not respond to the MP treatment. Of the patients thatresponded, 28% responded very slowly, 35% (19 males, 23 females) responded moderately, and 12% (8 males, 6 females) showed agood response to MP. For genotype analysis, we pooled 89 hypertensive patients and 71 controls. No association was found betweenCYP2D6*4 polymorphism and MP response.Conclusion: We found no relationship between MP response and CYP2D6*4 genotype in an Indian population in our study.

Anahtar Kelime:

Konular: Cerrahi

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık

1. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL, Jones DW, Materson BJ, Oparil S, Wright JT et al. Te Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure. JAMA 2003; 389: 25602572.
2. MacMahon SW, Wilcken DEL, Macdonald GJ. Te efect of weight reduction on lef ventricular mass: a randomized controlled trial in young overweight hypertensive patients. N Engl J Med 1986; 314: 334339.
3. Mohan V, Deepa M, Farooq S, Datta M, Deepa R. Prevalence, awareness and control of hypertension in Chennai--Te Chennai Urban Rural Epidemiology Study (CURES-52). J Assoc Physicians India 2007; 55: 326332.
4. Khan NA, Hemmelgan B, Padwal R, Larochelle P. The 2007 Canadian Hypertension Education programme recommendations for the management of hypertension. Can J Cardiol 2007; 23: 603604.
5. Eichelbaum M, Baur MP, Dengler HJ. Chromosomal assignment of human cytochrome P-450 (debrisoquine/ spartiene type) to chromosome 22. Br J Clin Pharmacol 1987; 23: 455458.
6. Mabic S, Castagnoli K, Castagnoli JN. Oxidative metabolic bioactivation of xenobiotics. In: Woolf TE, editor. Handbook of Drug Metabolism. New York, NY, USA: Marcel Dekker; 1999. pp. 4979.
7. Zanger UM, Fischer J, Raimundo S, Sturen T, Evert BO, Schwab M. Comprehensive analysis of the genetic factors determining expression and function of hepatic CYP 2D6. Pharmacogenetics 2001; 11: 573585.
8. Sachse C, Brockmöller J, Bauer S, Roots I. Cytochrome P450 2D6 variants in a Caucasian population: allele frequencies and phenotypic consequences. Am J Hum Genet 1977; 60: 284 295.
9. Daly AK. Molecular basis of polymorphic drug metabolism. J Mol Med 1995; 173: 539553.
10. Kirchheiner J, Heesch C, Bauer S, Meisel C, Seringer A, Goldammer M, Tzvetkov M, Meineke I, Roots I, Brockmüller J. Impact of the ultrarapid metabolizer genotype of cytochrome P450 2D6 on metoprolol pharmacokinetic and pharmacodynamics. Clin Pharmacol Ter 2004; 98: 302312.
11. Johnson AJ, Cavallari LH. Cardiovascular pharmacogenomics. Exp Physiol 2004; 90: 283289.
12. Sharma A, Pibarot P, Pilote S, Dumesnil JG, Arsenault M, Bélanger PM, Meibohm B, Hamelin BA. Toward optimal treatment in women: the efect of sex on metoprolol- diphenhydramine interaction. Clin Pharmacol 2010; 50: 214 225.
13. Jochmann N, Stangl K, Garbe E, Baumann G, Stangl V. Female-specifc aspects in the pharmacotherapy of chronic cardiovascular diseases. Eur Heart J 2005; 26: 15851595.
14. Veterans Administration Co-Operative Study Group on Antihypertensive Agents. Racial diferences in response to low dose captopril are abolished by the addition of hydrochlorothiazide. Br J Clinical Pharmacol 1982; 14: 97101.
15. Namath A, Chen C, Agrawal R. β1 and β2 Adrenergic receptor polymorphisms: their impact on cardiovascular physiology, diseased states and response to therapeutic agents. Seminars in Anesthesia, Perioperative Medicine and Pain 2007; 26: 29.
16. Materson BJ. Variability in response to antihypertensive drug treatment. Hypertension 2004; 43: 11661167.
17. Fredman RM. Metoprolol for hypertension. Open trial in general practice. Med J Aust 1982; 8: 378380.

APA	AYYAPPADHAS R, DHANALEKSHMI U, JESTIN C (2015). CYP 2D6*4 polymorphism and interindividual response variation to metoprolol in stage 1 hypertensive patients: no association in a rural Indian population?. , 352 - 357.
Chicago	AYYAPPADHAS Rajagopal,DHANALEKSHMI Unnikrishnan,JESTIN Chelliah CYP 2D6*4 polymorphism and interindividual response variation to metoprolol in stage 1 hypertensive patients: no association in a rural Indian population?. (2015): 352 - 357.
MLA	AYYAPPADHAS Rajagopal,DHANALEKSHMI Unnikrishnan,JESTIN Chelliah CYP 2D6*4 polymorphism and interindividual response variation to metoprolol in stage 1 hypertensive patients: no association in a rural Indian population?. , 2015, ss.352 - 357.
AMA	AYYAPPADHAS R,DHANALEKSHMI U,JESTIN C CYP 2D6*4 polymorphism and interindividual response variation to metoprolol in stage 1 hypertensive patients: no association in a rural Indian population?. . 2015; 352 - 357.
Vancouver	AYYAPPADHAS R,DHANALEKSHMI U,JESTIN C CYP 2D6*4 polymorphism and interindividual response variation to metoprolol in stage 1 hypertensive patients: no association in a rural Indian population?. . 2015; 352 - 357.
IEEE	AYYAPPADHAS R,DHANALEKSHMI U,JESTIN C "CYP 2D6*4 polymorphism and interindividual response variation to metoprolol in stage 1 hypertensive patients: no association in a rural Indian population?." , ss.352 - 357, 2015.
ISNAD	AYYAPPADHAS, Rajagopal vd. "CYP 2D6*4 polymorphism and interindividual response variation to metoprolol in stage 1 hypertensive patients: no association in a rural Indian population?". (2015), 352-357.

APA	AYYAPPADHAS R, DHANALEKSHMI U, JESTIN C (2015). CYP 2D6*4 polymorphism and interindividual response variation to metoprolol in stage 1 hypertensive patients: no association in a rural Indian population?. Turkish Journal of Medical Sciences, 45(2), 352 - 357.
Chicago	AYYAPPADHAS Rajagopal,DHANALEKSHMI Unnikrishnan,JESTIN Chelliah CYP 2D6*4 polymorphism and interindividual response variation to metoprolol in stage 1 hypertensive patients: no association in a rural Indian population?. Turkish Journal of Medical Sciences 45, no.2 (2015): 352 - 357.
MLA	AYYAPPADHAS Rajagopal,DHANALEKSHMI Unnikrishnan,JESTIN Chelliah CYP 2D6*4 polymorphism and interindividual response variation to metoprolol in stage 1 hypertensive patients: no association in a rural Indian population?. Turkish Journal of Medical Sciences, vol.45, no.2, 2015, ss.352 - 357.
AMA	AYYAPPADHAS R,DHANALEKSHMI U,JESTIN C CYP 2D6*4 polymorphism and interindividual response variation to metoprolol in stage 1 hypertensive patients: no association in a rural Indian population?. Turkish Journal of Medical Sciences. 2015; 45(2): 352 - 357.
Vancouver	AYYAPPADHAS R,DHANALEKSHMI U,JESTIN C CYP 2D6*4 polymorphism and interindividual response variation to metoprolol in stage 1 hypertensive patients: no association in a rural Indian population?. Turkish Journal of Medical Sciences. 2015; 45(2): 352 - 357.
IEEE	AYYAPPADHAS R,DHANALEKSHMI U,JESTIN C "CYP 2D6*4 polymorphism and interindividual response variation to metoprolol in stage 1 hypertensive patients: no association in a rural Indian population?." Turkish Journal of Medical Sciences, 45, ss.352 - 357, 2015.
ISNAD	AYYAPPADHAS, Rajagopal vd. "CYP 2D6*4 polymorphism and interindividual response variation to metoprolol in stage 1 hypertensive patients: no association in a rural Indian population?". Turkish Journal of Medical Sciences 45/2 (2015), 352-357.