The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

OCT2 polymorphisms and in-vivo renal functional consequence: studies with metformin and cimetidine.

PURPOSE: Genetic polymorphisms of organic cation transporter 2 (OCT2) have been recently described, but their genotype-phenotype relationship in humans is unknown. We performed this study to (i) characterize genetic variations of the OCT2 gene in the Chinese population and (ii) investigate the potential functional significance of OCT2 polymorphisms using metformin (an OCT2 substrate) alone or in the presence of its transport inhibitor (cimetidine). METHOD: Direct sequencing of all OCT2 exons and the surrounding introns was performed using genomic DNA from 112 healthy Chinese participants. To evaluate the potential functional change of a common 808G>T variant (Ala270Ser) identified in this population, 15 healthy participants with different 808G>T mutation status were recruited in a pharmacokinetic study of metformin with or without cimetidine. RESULTS: A total of 14 genetic variants were identified and 13 had frequency more than 1%. The renal tubular clearance (CLt) of metformin averaged 8.78+/-1.75, 7.68+/-0.672, and 6.32+/-0.954 ml/min/kg for participants with GG (n=6), GT (n=5), and TT (n=4) genotypes, respectively (P=0.037, one-way analysis of variance). In the presence of cimetidine, metformin CLt was decreased in all participants, but the decrease was significantly lower in TT than GG group (18.7 vs. 48.2%, P=0.029). CONCLUSION: Our study results demonstrated for the first time the existence of genetic polymorphisms of OCT2 in the Chinese population, and further showed that the 808G>T polymorphism is associated with a reduced metformin renal or tubular clearance. Moreover, the inhibition of metformin renal tubular secretion by cimetidine also appeared to be dependent on this mutation.[1]

References

  1. OCT2 polymorphisms and in-vivo renal functional consequence: studies with metformin and cimetidine. Wang, Z.J., Yin, O.Q., Tomlinson, B., Chow, M.S. Pharmacogenet. Genomics (2008) [Pubmed]
 
WikiGenes - Universities