title: Thiopurine methyltransferase genotype and phenotype status in Japanese patients with systemic lupus erythematosus.
abstract: We investigated the genotypic status of thiopurine methyltransferase (TPMT) polymorphism to evaluate the possible risk of the toxicity of azathioprine (AZA) in 68 patients with systemic lupus erythematosus (SLE). The allele frequency of TPMT mutation in the SLE group (2.9%) was higher than that in 174 Japanese healthy volunteers (1.1%), although it did not reach statistically significant difference (p=0.23). The mean value of TPMT activities in 51 subjects with TPMT*1/*1 was 40% higher than that of 4 subjects with TPMT*1/*3C in SLE group (18.1+/-6.1 nmol/h/ml packed red blood cells (pRBC) versus 13.2+/-3.2 nmol/h/ml pRBC; p=0.11). Two out of 4 SLE patients with TPMT*1/*3C had been treated with AZA, and one patient showed a leucopenia. The TPMT genotyping before AZA treatment is recommended for Japanese SLE patient group to avoid the AZA-induced adverse events, although detection of the patient with low TPMT activity by genotyping is still imperfect.
authors.affiliation: Department of Clinical Pharmacology, Gunma University Graduate School of Medicine, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Okada
authors.forename: Katsunori
authors.initials: K
authors.lastname: Nakamura
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kodama
authors.forename: Kazue
authors.initials: K
authors.lastname: Ueki
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Tsukada
authors.forename: Akira
authors.initials: A
authors.lastname: Maezawa
authors.forename: Norifumi
authors.initials: N
authors.lastname: Tsukamoto
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Nojima
authors.forename: Takashi
authors.initials: T
authors.lastname: Ishizaki
authors.forename: Ryuya
authors.initials: R
authors.lastname: Horiuchi
authors.forename: Koujirou
authors.initials: K
authors.lastname: Yamamoto
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D001379:Azathioprine / Q000627:therapeutic use; D004247:DNA / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007564:Japan / Q000453:epidemiology; D008180:Lupus Erythematosus, Systemic / Q000201:enzymology* / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008780:Methyltransferases / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D007166:Immunosuppressive Agents; D004247:DNA; D008780:Methyltransferases; C022745:thiopurine methyltransferase; D001379:Azathioprine