Acetylator phenotype and genotype in patients infected with HIV: Discordance between methods for phenotype determination and genotype

William M. O'Neil, Robert K. Drobitch, Rodger David MacArthur, Marti J. Farrough, Mark A. Doll, Adrian J. Fretland, David W. Hein, Lawrence R. Crane, Craig K. Svensson

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

The acetylator phenotype and genotype of AIDS patients, with and without an acute illness, was compared with that of healthy control subjects (30 per group). Two probe drugs, caffeine and dapsone, were used to determine the phenotype in the acutely ill cohort. Polymerase chain reaction amplification and restriction fragment length polymorphism analysis served to distinguish between the 26 known NAT2 alleles and the 21 most common NAT1 alleles. The distribution (%) of slow:rapid acetylator phenotype seen among acutely ill AIDS patients differed with the probe substrate used: 70:30 with caffeine versus 53:47 with dapsone. Phenotype assignment differed considerably between the two methods and there were numerous discrepancies between phenotype and genotype. The NAT2 genotype distribution was 45:55 slow:rapid. Control subjects, phenotyped only with caffeine, were 67:33 slow:rapid versus 60:40 genotypically. Stable AIDS patients, phenotyped only with dapsone, were 55:45 slow:rapid versus 46:54 genotypically. Following resolution of their acute infections, 12 of the acutely ill subjects were rephenotyped with dapsone. Phenotype assignment remained unchanged in all cases. The distribution of NAT1 alleles was similar in all three groups. It is evident from the amount of discordance between caffeine phenotype and dapsone phenotype or genotype that caution should be exercised in the use of caffeine as a probe for NAT2 in acutely ill patients. It is also clear that meaningful study of the acetylation polymorphism requires both phenotypic and genotypic data. (C) 2000 Lippincott Williams and Wilkins.

Original languageEnglish (US)
Pages (from-to)171-182
Number of pages12
JournalPharmacogenetics
Volume10
Issue number2
DOIs
StatePublished - Jan 1 2000
Externally publishedYes

Fingerprint

Genotyping Techniques
Dapsone
Genotype
HIV
Phenotype
Caffeine
Acquired Immunodeficiency Syndrome
Alleles
Acetylation
Restriction Fragment Length Polymorphisms
Healthy Volunteers
Polymerase Chain Reaction

Keywords

  • Arylamine N-acetyltransferase
  • Genotype
  • HIV infections/acquired immunodeficiency syndrome
  • Phenotype

ASJC Scopus subject areas

  • Genetics
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Acetylator phenotype and genotype in patients infected with HIV : Discordance between methods for phenotype determination and genotype. / O'Neil, William M.; Drobitch, Robert K.; MacArthur, Rodger David; Farrough, Marti J.; Doll, Mark A.; Fretland, Adrian J.; Hein, David W.; Crane, Lawrence R.; Svensson, Craig K.

In: Pharmacogenetics, Vol. 10, No. 2, 01.01.2000, p. 171-182.

Research output: Contribution to journalArticle

O'Neil, William M. ; Drobitch, Robert K. ; MacArthur, Rodger David ; Farrough, Marti J. ; Doll, Mark A. ; Fretland, Adrian J. ; Hein, David W. ; Crane, Lawrence R. ; Svensson, Craig K. / Acetylator phenotype and genotype in patients infected with HIV : Discordance between methods for phenotype determination and genotype. In: Pharmacogenetics. 2000 ; Vol. 10, No. 2. pp. 171-182.
@article{7b1eb8034acf43369d6b8edb9678b75d,
title = "Acetylator phenotype and genotype in patients infected with HIV: Discordance between methods for phenotype determination and genotype",
abstract = "The acetylator phenotype and genotype of AIDS patients, with and without an acute illness, was compared with that of healthy control subjects (30 per group). Two probe drugs, caffeine and dapsone, were used to determine the phenotype in the acutely ill cohort. Polymerase chain reaction amplification and restriction fragment length polymorphism analysis served to distinguish between the 26 known NAT2 alleles and the 21 most common NAT1 alleles. The distribution ({\%}) of slow:rapid acetylator phenotype seen among acutely ill AIDS patients differed with the probe substrate used: 70:30 with caffeine versus 53:47 with dapsone. Phenotype assignment differed considerably between the two methods and there were numerous discrepancies between phenotype and genotype. The NAT2 genotype distribution was 45:55 slow:rapid. Control subjects, phenotyped only with caffeine, were 67:33 slow:rapid versus 60:40 genotypically. Stable AIDS patients, phenotyped only with dapsone, were 55:45 slow:rapid versus 46:54 genotypically. Following resolution of their acute infections, 12 of the acutely ill subjects were rephenotyped with dapsone. Phenotype assignment remained unchanged in all cases. The distribution of NAT1 alleles was similar in all three groups. It is evident from the amount of discordance between caffeine phenotype and dapsone phenotype or genotype that caution should be exercised in the use of caffeine as a probe for NAT2 in acutely ill patients. It is also clear that meaningful study of the acetylation polymorphism requires both phenotypic and genotypic data. (C) 2000 Lippincott Williams and Wilkins.",
keywords = "Arylamine N-acetyltransferase, Genotype, HIV infections/acquired immunodeficiency syndrome, Phenotype",
author = "O'Neil, {William M.} and Drobitch, {Robert K.} and MacArthur, {Rodger David} and Farrough, {Marti J.} and Doll, {Mark A.} and Fretland, {Adrian J.} and Hein, {David W.} and Crane, {Lawrence R.} and Svensson, {Craig K.}",
year = "2000",
month = "1",
day = "1",
doi = "10.1097/00008571-200003000-00009",
language = "English (US)",
volume = "10",
pages = "171--182",
journal = "Pharmacogenetics and Genomics",
issn = "1744-6872",
publisher = "Lippincott Williams and Wilkins",
number = "2",

}

TY - JOUR

T1 - Acetylator phenotype and genotype in patients infected with HIV

T2 - Discordance between methods for phenotype determination and genotype

AU - O'Neil, William M.

AU - Drobitch, Robert K.

AU - MacArthur, Rodger David

AU - Farrough, Marti J.

AU - Doll, Mark A.

AU - Fretland, Adrian J.

AU - Hein, David W.

AU - Crane, Lawrence R.

AU - Svensson, Craig K.

PY - 2000/1/1

Y1 - 2000/1/1

N2 - The acetylator phenotype and genotype of AIDS patients, with and without an acute illness, was compared with that of healthy control subjects (30 per group). Two probe drugs, caffeine and dapsone, were used to determine the phenotype in the acutely ill cohort. Polymerase chain reaction amplification and restriction fragment length polymorphism analysis served to distinguish between the 26 known NAT2 alleles and the 21 most common NAT1 alleles. The distribution (%) of slow:rapid acetylator phenotype seen among acutely ill AIDS patients differed with the probe substrate used: 70:30 with caffeine versus 53:47 with dapsone. Phenotype assignment differed considerably between the two methods and there were numerous discrepancies between phenotype and genotype. The NAT2 genotype distribution was 45:55 slow:rapid. Control subjects, phenotyped only with caffeine, were 67:33 slow:rapid versus 60:40 genotypically. Stable AIDS patients, phenotyped only with dapsone, were 55:45 slow:rapid versus 46:54 genotypically. Following resolution of their acute infections, 12 of the acutely ill subjects were rephenotyped with dapsone. Phenotype assignment remained unchanged in all cases. The distribution of NAT1 alleles was similar in all three groups. It is evident from the amount of discordance between caffeine phenotype and dapsone phenotype or genotype that caution should be exercised in the use of caffeine as a probe for NAT2 in acutely ill patients. It is also clear that meaningful study of the acetylation polymorphism requires both phenotypic and genotypic data. (C) 2000 Lippincott Williams and Wilkins.

AB - The acetylator phenotype and genotype of AIDS patients, with and without an acute illness, was compared with that of healthy control subjects (30 per group). Two probe drugs, caffeine and dapsone, were used to determine the phenotype in the acutely ill cohort. Polymerase chain reaction amplification and restriction fragment length polymorphism analysis served to distinguish between the 26 known NAT2 alleles and the 21 most common NAT1 alleles. The distribution (%) of slow:rapid acetylator phenotype seen among acutely ill AIDS patients differed with the probe substrate used: 70:30 with caffeine versus 53:47 with dapsone. Phenotype assignment differed considerably between the two methods and there were numerous discrepancies between phenotype and genotype. The NAT2 genotype distribution was 45:55 slow:rapid. Control subjects, phenotyped only with caffeine, were 67:33 slow:rapid versus 60:40 genotypically. Stable AIDS patients, phenotyped only with dapsone, were 55:45 slow:rapid versus 46:54 genotypically. Following resolution of their acute infections, 12 of the acutely ill subjects were rephenotyped with dapsone. Phenotype assignment remained unchanged in all cases. The distribution of NAT1 alleles was similar in all three groups. It is evident from the amount of discordance between caffeine phenotype and dapsone phenotype or genotype that caution should be exercised in the use of caffeine as a probe for NAT2 in acutely ill patients. It is also clear that meaningful study of the acetylation polymorphism requires both phenotypic and genotypic data. (C) 2000 Lippincott Williams and Wilkins.

KW - Arylamine N-acetyltransferase

KW - Genotype

KW - HIV infections/acquired immunodeficiency syndrome

KW - Phenotype

UR - http://www.scopus.com/inward/record.url?scp=0034105165&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034105165&partnerID=8YFLogxK

U2 - 10.1097/00008571-200003000-00009

DO - 10.1097/00008571-200003000-00009

M3 - Article

C2 - 10762005

AN - SCOPUS:0034105165

VL - 10

SP - 171

EP - 182

JO - Pharmacogenetics and Genomics

JF - Pharmacogenetics and Genomics

SN - 1744-6872

IS - 2

ER -