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

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)2072-2078
Number of pages7
JournalAmerican Journal of Health-System Pharmacy
Volume69
Issue number23
DOIs
Publication statusPublished - 2012 Dec 1
Externally publishedYes

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Azathioprine
Genetic Polymorphisms
Systemic Lupus Erythematosus
Single Nucleotide Polymorphism
Alleles
DNA

ASJC Scopus subject areas

  • Pharmacology
  • Health Policy

Cite this

Effect of genetic polymorphisms on effectiveness of low-dose azathioprine in Japanese patients with systemic lupus erythematosus. / Nagamine, Ayumu; Takenaka, Miki; Aomori, Tohru; Okada, Yuko; Hiromura, Keiju; Nojima, Yoshihisa; Araki, Takuya; Nakamura, Tomonori; Yamamoto, Koujirou.

In: American Journal of Health-System Pharmacy, Vol. 69, No. 23, 01.12.2012, p. 2072-2078.

Research output: Contribution to journalArticle

Nagamine, Ayumu ; Takenaka, Miki ; Aomori, Tohru ; Okada, Yuko ; Hiromura, Keiju ; Nojima, Yoshihisa ; Araki, Takuya ; Nakamura, Tomonori ; Yamamoto, Koujirou. / Effect of genetic polymorphisms on effectiveness of low-dose azathioprine in Japanese patients with systemic lupus erythematosus. In: American Journal of Health-System Pharmacy. 2012 ; Vol. 69, No. 23. pp. 2072-2078.
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abstract = "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.",
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T1 - Effect of genetic polymorphisms on effectiveness of low-dose azathioprine in Japanese patients with systemic lupus erythematosus

AU - Nagamine, Ayumu

AU - Takenaka, Miki

AU - Aomori, Tohru

AU - Okada, Yuko

AU - Hiromura, Keiju

AU - Nojima, Yoshihisa

AU - Araki, Takuya

AU - Nakamura, Tomonori

AU - Yamamoto, Koujirou

PY - 2012/12/1

Y1 - 2012/12/1

N2 - 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.

AB - 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.

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