Relationship between genetic polymorphisms and mRNA expression of dihydrofolate reductase enzyme in a healthy Japanese population

Masayuki Hashiguchi, Mikiko Shimizu, Osamu Takeuchi, Tomoko Hayashi, Sachie Inoue, Takanori Tanaka, Tomonori Tsuru, Shin Irie, Tatsuo Kurokawa, Mayumi Mochizuki

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Aim: We aimed to investigate the relationship between genetic polymorphisms and mRNA expression of dihydrofolate reductase (DHFR) in a healthy Japanese population. Method: Two gene polymorphisms of DHFR(19-bp deletion allele and 3'UTR 829C>T) and mRNA expression of DHFR were evaluated in 100 unrelated healthy Japanese adults(47 men and 53 women). The genotype for DHFR 19-bp deletion was determined using the complete deletion/insertion method and that for DHFR 3'UTR 829C>T using the PCR-restriction fragment length polymorphism method. The mRNA expression of DHFR was determined by real-time PCR using RNA extracted from peripheral blood mononuclear cells. Results: Allelic frequencies of DHFR 19-bp deletion in healthy Japanese adults were: wild allele 38% and deletion allele 62%. Allelic frequencies of DHFR 3'UTR 829C>T were: C allele 83% and T allele 17%. Median (25th-75th percentile) mRNA expression levels of DHFR intron 1 in wild/wild, wild/deletion, and deletion/deletion individuals were 0.53 (0.33-0.61), 0.28 (0.20-0.44), and 0.33 (0.24-0.52), respectively, with a significant difference between wild/wild and wild/deletion (P = 0.010). Median mRNA expression of DHFR 3'UTR 829C>T in C/C and C/T genotypes were 0.29(0.20-0.45) and 0.41(0.25-0.62), respectively, with a significant difference between C/C and C/T(P=0.024). Conclusion: Our healthy Japanese adults showed statistically significant differences in distribution of allelic frequencies for DHFR 19-bp deletion and 3'UTR 829C>T, and in mRNA expression of DHFR according to genotype. Therefore, the genetic polymorphisms and/or differences in mRNA expression of DHFR might contribute to the variation in efficacy and toxicity of methotrexate in patients with rheumatoid arthritis and other diseases.

Original languageEnglish
Pages (from-to)185-192
Number of pages8
JournalJapanese Journal of Clinical Pharmacology and Therapeutics
Issue number3
Publication statusPublished - 2013 May 1



  • Dihydrofolate reductase
  • Genetic polymorphism
  • Healthy Japanese population
  • MRNA expression
  • Methotrexate

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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