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Titolo:
Polymorphisms of NAT2 in relation to sulphasalazine-induced agranulocytosis
Autore:
Wadelius, M; Stjernberg, E; Wiholm, BE; Rane, A;
Indirizzi:
Univ Uppsala Hosp, Dept Med Sci, S-75185 Uppsala, Sweden Univ Uppsala Hosp Uppsala Sweden S-75185 ed Sci, S-75185 Uppsala, Sweden Med Prod Agcy, Uppsala, Sweden Med Prod Agcy Uppsala SwedenMed Prod Agcy, Uppsala, Sweden
Titolo Testata:
PHARMACOGENETICS
fascicolo: 1, volume: 10, anno: 2000,
pagine: 35 - 41
SICI:
0960-314X(200002)10:1<35:PONIRT>2.0.ZU;2-K
Fonte:
ISI
Lingua:
ENG
Soggetto:
ARYLAMINE N-ACETYLTRANSFERASE; RHEUMATOID-ARTHRITIS; ACETYLATOR PHENOTYPE; CHROMOSOMAL LOCALIZATION; DRUG-METABOLISM; SULFASALAZINE; TOXICITY; IDENTIFICATION; PENICILLAMINE; MUTATIONS;
Keywords:
NAT2; polymorphism; sulphasalazine; agranulocytosis;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
37
Recensione:
Indirizzi per estratti:
Indirizzo: Wadelius, M Univ Uppsala Hosp, Dept Med Sci, S-75185 Uppsala, Sweden Univ Uppsala Hosp Uppsala Sweden S-75185 185 Uppsala, Sweden
Citazione:
M. Wadelius et al., "Polymorphisms of NAT2 in relation to sulphasalazine-induced agranulocytosis", PHARMACOGEN, 10(1), 2000, pp. 35-41

Abstract

Agranulocytosis is a rare, but serious adverse reaction to sulphasalazine,The polymorphic enzyme N-acetyltransferase 2 (NAT2) plays an important role in the metabolism of sulphasalazine. This study was conducted to analyse whether the risk of sulphasalazine-induced agranulocytosis is increased in slow acetylators. Patients were treated for inflammatory disease, mostly joint disease, with a mean dose of 2 g sulphasalazine daily. Thirty-nine patients reacted with agranulocytosis, while 75 patients had been treated for aminimum of 3 months without haematological side-effects. A population-based control panel of 448 individuals was used for comparison. All subjects were genotyped for NAT2 by polymerase chain reaction followed by restriction enzyme digestion. The six most common allelic variants were analysed: NAT2*4, NAT2*5A, NAT2*5B, NAT2*5C, NAT2*6 and NAT2*7. The proportion of slow acetylators was significantly higher in patients with sulphasalazine-induced agranulocytosis (69%) and population-based controls (64%) compared to patients who tolerated sulphasalazine (45%); odds ratio 2.71 [95% confidence interval (CI) 1.20; 6.15], P = 0.015, and odds ratio 2.17 (95% CI 1.32; 3.56), P = 0.002, respectively. Patients who developed agranulocytosis did not differ from population-based control subjects in the frequency of slow acetylators; odds ratio 1.25 (95% CI 0.62; 2.53), P = 0.535. The risk of agranulocytosis did not appear to be increased in slow acetylators, provided that the difference compared with sulphasalazine-treated control subjects was not due to a predominance of fast acetylators among patients with inflammatory joint disease. Instead, selection bias was suspected since more slow acetylators may have discontinued sulphasalazine therapy because of drug-intolerance. Pharmacogenetics 10:35-41 (C) 2000 Lippincott Williams & Wilkins.

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Documento generato il 01/04/20 alle ore 20:52:22