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

Background/aim: Genetic polymorphism of CYP2D6 shows diverse pharmacokinetic and pharmacodynamic variation. Therefore, the present work was designed to study the variation in therapeutic responses to metoprolol (MP) in stage 1 hypertensive patients and also aims to verify the association of CYP2D6*4 polymorphism and response variation in an Indian population for the first time. Materials and methods: Clinically, a total of 119 hypertensive patients and 116 healthy individuals as controls were included. Patients were treated with MP extended release 25 mg tablets once daily for 2 weeks. Reduction in systolic blood pressure, diastolic blood pressure, and pulse rate were recorded before and after the treatment. For genotyping, genotypes of 89 hypertensive patients and 71 healthy 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 that responded, 28% responded very slowly, 35% (19 males, 23 females) responded moderately, and 12% (8 males, 6 females) showed a good response to MP. For genotype analysis, we pooled 89 hypertensive patients and 71 controls. No association was found between CYP2D6*4 polymorphism and MP response. Conclusion: We found no relationship between MP response and CYP2D6*4 genotype in an Indian population in our study.

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

Background/aim: Genetic polymorphism of CYP2D6 shows diverse pharmacokinetic and pharmacodynamic variation. Therefore, the present work was designed to study the variation in therapeutic responses to metoprolol (MP) in stage 1 hypertensive patients and also aims to verify the association of CYP2D6*4 polymorphism and response variation in an Indian population for the first time. Materials and methods: Clinically, a total of 119 hypertensive patients and 116 healthy individuals as controls were included. Patients were treated with MP extended release 25 mg tablets once daily for 2 weeks. Reduction in systolic blood pressure, diastolic blood pressure, and pulse rate were recorded before and after the treatment. For genotyping, genotypes of 89 hypertensive patients and 71 healthy 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 that responded, 28% responded very slowly, 35% (19 males, 23 females) responded moderately, and 12% (8 males, 6 females) showed a good response to MP. For genotype analysis, we pooled 89 hypertensive patients and 71 controls. No association was found between CYP2D6*4 polymorphism and MP response. Conclusion: We found no relationship between MP response and CYP2D6*4 genotype in an Indian population in our study.

___

  • Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL, Jones DW, Materson BJ, Oparil S, Wright JT et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure. JAMA 2003; 389: 2560–2572.
  • 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: 603–604.
  • 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: 455–458.
  • 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. 49–79.
  • 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: 573–585.
  • 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: 539–553.
  • 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 Ther 2004; 98: 302–312.
  • Johnson AJ, Cavallari LH. Cardiovascular pharmacogenomics. Exp Physiol 2004; 90: 283–289.
  • Sharma A, Pibarot P, Pilote S, Dumesnil JG, Arsenault M, Bélanger PM, Meibohm B, Hamelin BA. Toward optimal treatment in women: the effect of sex on metoprolol- diphenhydramine interaction. Clin Pharmacol 2010; 50: 214– 225.
  • Jochmann N, Stangl K, Garbe E, Baumann G, Stangl V. Female-specific aspects in the pharmacotherapy of chronic cardiovascular diseases. Eur Heart J 2005; 26: 1585–1595.
  • Veterans Administration Co-Operative Study Group on Antihypertensive Agents. Racial differences in response to low dose captopril are abolished by the addition of hydrochlorothiazide. Br J Clinical Pharmacol 1982; 14: 97–101.
  • 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: 2–9.
  • Materson BJ. Variability in response to antihypertensive drug treatment. Hypertension 2004; 43: 1166–1167.
  • Fredman RM. Metoprolol for hypertension. Open trial in general practice. Med J Aust 1982; 8: 378–380.
Turkish Journal of Medical Sciences-Cover
  • ISSN: 1300-0144
  • Yayın Aralığı: 6
  • Yayıncı: TÜBİTAK
Sayıdaki Diğer Makaleler

Protective effect of \beta-glucan on acute lung injury induced by lipopolysaccharide in rats

MERYEM IRAZ, MUSTAFA IRAZ, MUKADDES EŞREFOĞLU, MEHMET ŞERİF AYDIN

The impact of one fraction of 8 Gy radiotherapy in palliative treatment of multiple myeloma patients with painful bone destructions

Milda RUDZIANSKIENE, ARTURAS INCIURA, ELONA JUOZAITYTE, Rolandas GERBUTAVICIUS, Renata SIMOLIUNIENE, Viktoras RUDZIANSKAS, Greta Emilia KIAVIALAITIS

What primary care physicians think about insulin initiation in type 2 diabetes: a feld-based study

Yaşar KOŞAR, Mustafa Haki SUCAKLI, Muharrem AK, Metin CANBAL

Evaluation of children presenting to the emergency room afer electrical injury

Sibel ÇELİK, Nesibe ANDIRAN, Mine GÜVELOĞLU, Gülten KÜÇÜKKONYALI, Yasemin İNAN, Ali Osman KÖKSAL, Mehtap ACAR, Sacit GÜNBEY, Osman ÖZDEMİR, Aslıhan YILMAZ ARASLI

Effectiveness of pelvic floor muscle training on symptoms and uroflowmetry parameters in female patients with overactive bladder

Haluk KULAKSIZOĞLU, Murat AKAND, Evrim ÇAKMAKÇI, Murat GÜL, Bedreddin SEÇKİN

Premarital screening of 466 Mediterranean women for serum ferritin, vitamin B12, and folate concentrations

AYSUN KARABULUT, ÖMER TOLGA GÜLER, HATİCE TUBA KARAHAN, SEVGİ ÖZKAN, HASAN KOYUNCU, İBRAHİM DEMİRCİLER

Effect of keratinocyte growth factor on growth and transdifferentiation of primary alveolar epithelial type II cells

Xiuxiang LIU, ZHICHUN FENG, Chunmei TIAN, Xiangyong KONG, YUMEI WU, Changjun LV

The effects of prenatal long-duration exposure to 900-MHz electromagnetic field on the 21-day-old newborn male rat liver

ZEHRA TOPAL, HATİCE HANCI, TOLGA MERCANTEPE, HÜSEYİN SERKAN EROL, OSMAN NURİ KELEŞ, HAYDAR KAYA, SEVDEGÜL MUNGAN, ERSAN ODACI

The effects of atorvastatin on antioxidant/antiinflammatory properties of HDLs in hypercholesterolemics

GÜLŞEN AKALIN ÇİFTÇİ, İPEK ERTORUN, AYSEN AKALIN, İBRAHİM ÖZKAN ALATAŞ, AHMET MUSMUL

Quantitative study of epigenetic signature in head >and neck squamous cell carcinoma

Ayesha UMAIR, Bassel TARAKJI, Alzoghaibi IBRAHIM, Azzeghaibi NASSER, Alenzi FQ, Ayesha SHREEN