Document Detail


Human organic cation transporter (OCT1 and OCT2) gene polymorphisms and therapeutic effects of metformin.
MedLine Citation:
PMID:  17111267     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Eriko Shikata; Rei Yamamoto; Hiroshi Takane; Chiaki Shigemasa; Tadasu Ikeda; Kenji Otsubo; Ichiro Ieiri
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-11-17
Journal Detail:
Title:  Journal of human genetics     Volume:  52     ISSN:  1434-5161     ISO Abbreviation:  J. Hum. Genet.     Publication Date:  2007  
Date Detail:
Created Date:  2007-01-30     Completed Date:  2007-03-13     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9808008     Medline TA:  J Hum Genet     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  117-22     Citation Subset:  IM    
Affiliation:
Department of Hospital Pharmacy, Tottori University, Yonago, Japan.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Diabetes Mellitus, Type 2 / drug therapy*,  genetics
Female
Humans
Hypoglycemic Agents / therapeutic use*
Male
Metformin / therapeutic use*
Middle Aged
Organic Cation Transport Proteins / genetics*,  metabolism
Organic Cation Transporter 1 / genetics*,  metabolism
Polymerase Chain Reaction
Polymorphism, Genetic*
Polymorphism, Single-Stranded Conformational
RNA, Messenger / metabolism
Chemical
Reg. No./Substance:
0/Hypoglycemic Agents; 0/Organic Cation Transport Proteins; 0/Organic Cation Transporter 1; 0/RNA, Messenger; 0/SLC22A2 protein, human; 657-24-9/Metformin

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