Human organic cation transporter (OCT1 and OCT2) gene polymorphisms and therapeutic effects of metformin

Eriko Shikata, Rei Yamamoto, Hiroshi Takane, Chiaki Shigemasa, Tadasu Ikeda, Kenji Otsubo, Ichiro Ieiri

研究成果: Contribution to journalArticle査読

152 被引用数 (Scopus)

抄録

Organic cation transporters (OCTs) are responsible for the hepatic and renal transport of metformin. In this study we analyzed variants of OCT1 and OCT2 genes in 33 patients (24 responders and nine non-responders) based on the hypothesis that polymorphisms in both genes contribute to large inter-patient variability in the clinical efficacy of metformin. The sequences of the 5′-flanking and coding regions of the two genes of interest were screened by single-strand conformation polymorphism (SSCP) analysis. To compare the causative factors between responders and non-responders, we performed stepwise discriminant functional analysis. Age, body mass index (BMI) and treatment with lipid-lowering agents were demonstrated as positive predictors, and two mutations in the OCT1 gene, -43T > G in intron 1 and 408Met > Val (1222A > G) in exon 7, were negative and positive predictors, respectively, for the efficacy of metformin; the predictive accuracy was 55.5% (P < 0.05). Subsequent study indicated that OCT1 mRNA levels tended to be lower in human livers with the 408Met (1222A) variant, though the differences did not reach the level of significance. In this study it is suggested that OCT1 and OCT2 gene polymorphisms have little contribution to the clinical efficacy of metformin.

本文言語英語
ページ(範囲)117-122
ページ数6
ジャーナルJournal of Human Genetics
52
2
DOI
出版ステータス出版済み - 2 2007

All Science Journal Classification (ASJC) codes

  • 遺伝学
  • 遺伝学(臨床)

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