title: Effect of genetic polymorphisms on effectiveness of low-dose azathioprine in Japanese patients with systemic lupus erythematosus.
abstract: OBJECTIVE
  The effect of genetic polymorphisms on the effectiveness of low-dose azathioprine in Japanese patients with systemic lupus erythematosus (SLE) was studied.
  
  
  METHODS
  Sixty-one unrelated Japanese patients with SLE treated with azathioprine were included in the study. The selected genetic polymorphisms evaluated in the analysis were ITPA 138G>A, ITPA 563G>A, IMPDH 1575A>G, XO 837C>T, XO 2211C>T, XO 3030C>T, and MRP4 2269G>A. The DNA isolation and genotyping procedures for ITPA 94C>A and TPMT*3C were the same as those in a previous study. Genotyping of ITPA 138G>A, ITPA 563G>A, IMPDH 1575A>G, MRP4 2269G>A, XO 837C>T, XO 2211C>T, and XO 3030C>T was performed using a validated genotyping assay. The SLE disease activity index (SLEDAI) score was used as a marker for the efficacy of azathioprine treatment, and the correlations between the changes in the SLEDAI score and the considered polymorphisms were evaluated.
  
  
  RESULTS
  The mean SLE duration, SLEDAI score, and azathioprine dosage prescribed were 5.6 years, 6.0, and 1 mg/kg/day, respectively. Small (but not significant) p values suggested a tendency for the reduction in the SLEDAI score to be greater in patients with the ITPA 94A allele. Further, the ITPA 94C>A polymorphism correlated highly with the change in the SLEDAI score. However, there were no significant associations among TPMT*3C, ITPA 138G>A, ITPA 563G>A, IMPDH 1575A>G, XO 837C>T, XO 2211C>T, and XO 3030C>T and the mean changes in the SLEDAI score over the one-year investigation period.
  
  
  CONCLUSIONS
  The ITPA 94C>A polymorphism was found to possibly influence the clinical response to low-dose azathioprine in Japanese patients with SLE. The other studied single-nucleotide polymorphisms appeared to have little influence on the effectiveness of azathioprine.
authors.affiliation: Department of Pharmacy, Gunma University Hospital, Showa-machi, Maebashi, Japan.
authors.forename: Ayumu
authors.initials: A
authors.lastname: Nagamine
authors.forename: Miki
authors.initials: M
authors.lastname: Takenaka
authors.forename: Tohru
authors.initials: T
authors.lastname: Aomori
authors.forename: Yuko
authors.initials: Y
authors.lastname: Okada
authors.forename: Keiju
authors.initials: K
authors.lastname: Hiromura
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Nojima
authors.forename: Takuya
authors.initials: T
authors.lastname: Araki
authors.forename: Tomonori
authors.initials: T
authors.lastname: Nakamura
authors.forename: Koujirou
authors.initials: K
authors.lastname: Yamamoto
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D001379:Azathioprine / Q000627:therapeutic use*; D005260:Female; D005838:Genotype; D006801:Humans; D007168:IMP Dehydrogenase / Q000235:genetics; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011755:Pyrophosphatases / Q000235:genetics; D012189:Retrospective Studies; D012720:Severity of Illness Index; D014969:Xanthine Oxidase / Q000235:genetics; D000097630:Inosine Triphosphatase
chemical_list: D001379:Azathioprine; D007168:IMP Dehydrogenase; D007166:Immunosuppressive Agents; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D011755:Pyrophosphatases; D014969:Xanthine Oxidase; C073492:ABCC4 protein, human; C511829:ITPA protein, human; D000097630:Inosine Triphosphatase