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.
| Original language | English |
|---|---|
| Pages (from-to) | 117-122 |
| Number of pages | 6 |
| Journal | Journal of Human Genetics |
| Volume | 52 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Feb 1 2007 |
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All Science Journal Classification (ASJC) codes
- Genetics
- Genetics(clinical)
Cite this
Human organic cation transporter (OCT1 and OCT2) gene polymorphisms and therapeutic effects of metformin. / Shikata, Eriko; Yamamoto, Rei; Takane, Hiroshi; Shigemasa, Chiaki; Ikeda, Tadasu; Otsubo, Kenji; Ieiri, Ichiro.
In: Journal of Human Genetics, Vol. 52, No. 2, 01.02.2007, p. 117-122.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Human organic cation transporter (OCT1 and OCT2) gene polymorphisms and therapeutic effects of metformin
AU - Shikata, Eriko
AU - Yamamoto, Rei
AU - Takane, Hiroshi
AU - Shigemasa, Chiaki
AU - Ikeda, Tadasu
AU - Otsubo, Kenji
AU - Ieiri, Ichiro
PY - 2007/2/1
Y1 - 2007/2/1
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=33846617263&partnerID=8YFLogxK
U2 - 10.1007/s10038-006-0087-0
DO - 10.1007/s10038-006-0087-0
M3 - Article
C2 - 17111267
AN - SCOPUS:33846617263
VL - 52
SP - 117
EP - 122
JO - Journal of Human Genetics
JF - Journal of Human Genetics
SN - 1434-5161
IS - 2
ER -