Pharmacogentic study of methyleneterahyrofolate reductase and thymidylate synthase in Japanese and assessment of ethnic and gender differences

Sachie Inoue, Masayuki Hashiguchi, Takeshi Chiyoda, Yukiko Sunami, Takanori Tanaka, Mayumi Mochizuki

研究成果: Article査読

16 被引用数 (Scopus)

抄録

Objectives: We investigated the four polymorphisms of the 5,10-methylenetetrahydrofolate reductase (MTHFR) and thymidylate synthase (TYMS) genes that are related to the pharmacologically active sites of methotrexate for the treatment of rheumatoid arthritis in 102 healthy Japanese adults and assessed the possibility of ethnic and gender differences. Methods: Polymorphisms of MTHFR C677T, A1298C, the two or three 28-bp tandem repeats in the TYMS 5′-untranslated regions (UTR), and the 6-bp deletion/insertion in the TYMS 3′-UTR were measured using polymerase chain reaction with restriction fragment length polymorphism method. Published data on allelic frequencies by ethnic group and gender were collected from Medline. Results: Allelic frequencies in healthy Japanese adults were: MTHFR 677T allele 41%, MTHFR 1298C allele 22%, TYMS 5′-UTR 3R allele 84%, and TYMS 3′-UTR-6-bp allele 59%. Significant differences were found in the distribution of MTHFR C677T between black and Japanese populations, of TYMS 5′-UTR alleles between Caucasian or black and Japanese populations, and of TYMS 3′-UTR alleles between Caucasian and Japanese populations (p < 0.001). Moreover, a gender difference was found in TYMS 3′-UTR allelic frequency in Japanese (p = 0.015). Conclusion: Ethnic and gender variations in the distribution of these allelic frequencies may associate with the difference in the effects of methotrexate in rheumatoid arthritis patients.

本文言語English
ページ(範囲)41-47
ページ数7
ジャーナルPharmacogenomics
8
1
DOI
出版ステータスPublished - 2007 1 1

ASJC Scopus subject areas

  • 分子医療
  • 遺伝学
  • 薬理学

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