Effect of genetic polymorphisms on effectiveness of low-dose azathioprine in Japanese patients with systemic lupus erythematosus

Ayumu Nagamine, Miki Takenaka, Tohru Aomori, Yuko Okada, Keiju Hiromura, Yoshihisa Nojima, Takuya Araki, Tomonori Nakamura, Koujirou Yamamoto

研究成果: Article査読

7 被引用数 (Scopus)

抄録

Purpose. 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, SLE-DAI 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. Conclusion. 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.

本文言語English
ページ(範囲)2072-2078
ページ数7
ジャーナルAmerican Journal of Health-System Pharmacy
69
23
DOI
出版ステータスPublished - 2012 12月 1
外部発表はい

ASJC Scopus subject areas

  • 薬理学
  • 健康政策

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