Polymorphism in human organic cation transporters and metformin action.

Considerable interindividual variabilities in clinical efficacy and adverse events are sometimes recognized in the treatment of Type 2 diabetes mellitus with oral antihyperglycemic drugs. Metformin is the most commonly used biguanide in clinical practice, and also improves insulin resistance and reduces cardiovascular risk. However, certain patients taking metformin do not respond sufficiently.

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

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.

Taurine inhibits apoptosis by preventing formation of the Apaf-1/caspase-9 apoptosome.

Cardiomyocyte apoptosis contributes to cell death during myocardial infarction. One of the factors that regulate the degree of apoptosis during ischemia is the amino acid taurine. To study the mechanism underlying the beneficial effect of taurine, we examined the interaction between taurine and mitochondria-mediated apoptosis using a simulated ischemia model with cultured rat neonatal cardiomyocytes sealed in closed flasks.

Association of pharmacokinetic (CYP2C9) and pharmacodynamic (factors II, VII, IX, and X; proteins S and C; and gamma-glutamyl carboxylase) gene variants with warfarin sensitivity.

We analyzed mutations of 7 vitamin K-dependent protein and cytochrome P450 2C9 genes in 45 patients and investigated whether any contribute to the large interpatient variability in the warfarin dose-effect relationship. Total clearance and daily dose, INR and INR/Cp, were used as pharmacokinetic and pharmacodynamic indexes, respectively. Patients were grouped by genotype based on a single polymorphism and combinations of polymorphisms.