Human organic cation transporter (OCT1 and OCT2) gene polymorphisms and therapeutic effects of metformin.
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Shikata E, Yamamoto R, Takane H, Shigemasa C, Ikeda T, Otsubo K, Ieiri I
Human organic cation transporter (OCT1 and OCT2) gene polymorphisms and therapeutic effects of metformin.
J Hum Genet. 2007;52(2):117-22. Epub 2006 Nov 17.
- PubMed ID
- 17111267 [ View in PubMed]
- Abstract
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.