NAT2 genotyping and efficacy of sulfasalazine in patients with chronic discoid lupus erythematosus.
Sulfasalazine is an effective agent for chronic discoid lupus erythematosus (CDLE) but the response to treatment is considerably variable between patients and is also unpredictable. The reason for this might relate to differences in metabolism of the drug which is extensively acetylated by the polymorphic enzyme N-acetyltransferase 2 (NAT2). To test this possibility, the N-acetylation phenotype of eleven patients with CDLE and treated by standard doses of sulfasalazine was retrospectively determined by genotyping. A clear-cut difference in the outcome of treatment was observed according to whether the patients were slow acetylators (SA) or rapid acetylators (RA). Eight out of 11 patients responded to treatment with a complete or marked remission of the disease. Seven of them were RA. The three other patients who did not respond at all to the drug were SA. In addition, SA seem to be more prone to toxic events. These findings strongly suggest that the genetic polymorphism of NAT2 is responsible for differences in the response to sulfasalazine in patients with CDLE. Therefore, candidates for sulfasalazine therapy should be genotyped to identify those patients who might benefit from the drug.
Sabbagh
N
N
Laboratoire de Biochimie et Biologie Moléculaire de l'hôpital Calmette, Universitaire de Lille, France.
Delaporte
E
E
Marez
D
D
Lo-Guidice
J M
JM
Piette
F
F
Broly
F
F
D000107:Acetylation; D000328:Adult; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008179:Lupus Erythematosus, Discoid / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D012460:Sulfasalazine / Q000627:therapeutic use*
D012460:Sulfasalazine; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human