A family study of genetic and environmental factors determining polymorphic hydroxylation of debrisoquin

Clinical Pharmacology and Therapeutics
E SteinerF Sjöqvist

Abstract

Debrisoquin hydroxylation capacity determined as the ratio of debrisoquin to 4-OH-debrisoquin (DMR) in urine after a single oral dose (10 mg) was studied in 52 nuclear families comprising 226 subjects. The relative importance of genetic and environmental factors for DMR was studied by path analysis. There was a significant negative correlation between DMR and coffee intake but no significant correlations between DMR and sex, age, alcohol intake, or smoking habits. Path analysis showed that genetic heritability was 0.79 while cultural heritability was only 0.06. Complex segregation analysis gave evidence for a major locus with incomplete dominance (d = 0.28) between a recessive and an additive gene. The frequency of the major gene was 0.31, allowing an estimate of the frequency of slow hydroxylators in the Swedish population of 9.4%. There was also evidence for a multifactorial component accounting for 14% of the total variation. It was not possible to distinguish between the different genotypes within the rapid hydroxylator phenotype. Our data agree with previous studies in British and German populations showing that two alleles at a major autosomal locus can explain most of the observed variation in DMR. The frequency of slow ...Continue Reading

Citations

Jun 1, 1992·Journal of Internal Medicine·G Alván
Jan 1, 1991·European Journal of Clinical Pharmacology·E SpinaJ Benítez
Jan 1, 1990·British Journal of Clinical Pharmacology·C J SpeirsA R Boobis
Dec 1, 1989·British Journal of Clinical Pharmacology·Q Y YueJ Säwe
Feb 1, 1989·British Journal of Clinical Pharmacology·O MortimerA Rane
Jan 1, 1989·European Journal of Clinical Pharmacology·F DerenneP Bechtel
Jan 1, 1989·European Journal of Clinical Pharmacology·K Brøsen, L F Gram
Apr 1, 1987·Pharmacology & Toxicology·K BrøsenL Bertilsson
Apr 1, 1988·British Journal of Clinical Pharmacology·M EichelbaumC O Meese
Jan 1, 1987·Cancer Chemotherapy and Pharmacology·P A PhilipP G Harper
Jan 1, 1993·European Journal of Clinical Pharmacology·M L DahlF Sjöqvist
Apr 1, 1996·European Journal of Drug Metabolism and Pharmacokinetics·A LlerenaJ Benítez
Jun 27, 1998·British Journal of Clinical Pharmacology·L NybergM Nilsson
Aug 1, 1992·Molecular and Chemical Neuropathology·T Y LiuH C Liu
May 1, 1987·Diabetic Medicine : a Journal of the British Diabetic Association·S SjöbergJ Ostman
Jan 1, 1994·Fundamental & Clinical Pharmacology·C JoanneP Bechtel
May 20, 1998·Clinical Pharmacology and Therapeutics·P DalénL Bertilsson
Jan 1, 1994·European Journal of Clinical Pharmacology·K BrøsenK Skjødt
Jan 1, 1995·Cancer Chemotherapy and Pharmacology·L B AnthonyK R Hande
Oct 21, 1998·Therapeutic Drug Monitoring·Y Caraco
Jan 1, 1991·British Journal of Clinical Pharmacology·T D AriasR Barrantes
Sep 1, 1994·Journal of Clinical Pharmacology·D G May
Jun 1, 1989·British Journal of Industrial Medicine·G NiseP Orbaek
Jul 1, 1994·Pediatric Cardiology·T Paul, J Janousek
Oct 1, 1990·British Journal of Clinical Pharmacology·A R Boobis, D S Davies
Jan 1, 1990·Fundamental & Clinical Pharmacology·U A Meyer
Jan 1, 1990·European Journal of Clinical Pharmacology·G AlvánU Gundert-Remy
Jan 1, 1989·European Journal of Clinical Pharmacology·P A PhilipH J Rogers
Jan 1, 1991·European Journal of Clinical Pharmacology·J M LaderoM Díaz-Rubio
Dec 11, 2002·Journal of General Internal Medicine·Theodore W MarcyKimberly M Thompson
Jun 1, 1995·Journal of Clinical Psychopharmacology·H ArthurF Sjöqvist
Oct 1, 1993·Environmental Health Perspectives·A HirvonenH Vainio
Feb 3, 2007·European Journal of Clinical Pharmacology·D FrankU Fuhr
Apr 8, 2010·Journal of Medical Toxicology : Official Journal of the American College of Medical Toxicology·Hanna OvaskaPaul I Dargan
Jan 1, 2008·Anesthesia and Analgesia·Jeroen WinkJack W van Kleef
Aug 1, 1992·Acta Neurologica Scandinavica·M J SteigerP G Jenner
Jan 1, 1991·European Journal of Clinical Pharmacology·M E Veronese, S McLean
Jan 1, 1991·Fundamental & Clinical Pharmacology·G Alván
Oct 1, 1990·Pharmacology & Toxicology·M S Lennard
Nov 1, 1986·British Journal of Clinical Pharmacology·P R JacksonH F Woods
Oct 1, 1991·British Journal of Clinical Pharmacology·F BrolyM Lhermitte
Sep 1, 1986·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·E JacqzR A Branch
Jun 26, 2013·American Journal of Therapeutics·Eugene P Cleophas, Ton J Cleophas
Nov 1, 1988·British Journal of Clinical Pharmacology·P ArvelaO Pelkonen
Dec 1, 1989·British Journal of Clinical Pharmacology·Q Y YueJ Säwe
Jun 1, 1990·Annals of Medicine·J BenítezF González-Rozas
Mar 1, 1991·Acta Neurologica Scandinavica·J KallioE Syvälahti
Jun 27, 1998·British Journal of Clinical Pharmacology·U BangJ Viby-Mogensen
Jan 1, 1989·European Journal of Clinical Pharmacology·K Brøsen, L F Gram
Jul 1, 1993·Pharmacology & Toxicology·A LlerenaL Bertilsson
Jan 1, 1990·Pharmacology & Therapeutics·U A MeyerU M Zanger
Jan 1, 1989·Pharmacology & Therapeutics·M S Lennard

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