Structural Basis of Single-Nucleotide Polymorphisms in Cytochrome P450 2C9.

Single-nucleotide polymorphisms in drug-metabolizing cytochrome P450 (CYP) enzymes are important contributors to interindividual differences in drug metabolism leading to adverse drug reactions. Despite their extensive characterization and importance in pharmacogenetics of clinical drugs, the structural basis of CYP polymorphisms has remained scant. Here we report the crystal structures of human CYP2C9 and its polymorphic variants, *3 (I359L) and *30 (A477T), with an antihypertensive drug losartan.

A possible role for HLA-DRB1*04:06 in statin-related myopathy in Japanese patients.

Statin-related myopathy (SRM) is a clinically important adverse reaction. Recent pharmacogenetic research, mainly in non-Asian populations, have indicated clinical relevance of some of genetic biomarkers to SRM, but predictive markers for SRM in Asian populations including Japanese has not yet been established. This study was aimed to identify clinically important genetic markers associated with SRM in Japanese patients.

Different Results of IgE Binding- and Crosslinking-Based Allergy Tests Caused by Allergen Immobilization.

The physicochemical nature of allergen molecules differ from the liquid phase to the solid phase. However, conventional allergy tests are based on the detection of immunoglobulin (Ig)E binding to immobilized allergens. We recently developed an in vitro allergy testing method using a luciferase-reporting humanized rat mast cell line to detect IgE crosslinking-induced luciferase expression (EXiLE test).

Global metabolomic analysis of heart tissue in a hamster model for dilated cardiomyopathy.

Dilated cardiomyopathy (DCM), a common cause of heart failure, is characterized by cardiac dilation and reduced left ventricular ejection fraction, but the underlying mechanisms remain unclear. To investigate the mechanistic basis, we performed global metabolomic analysis of myocardial tissues from the left ventricles of J2N-k cardiomyopathic hamsters. This model exhibits symptoms similar to those of human DCM, owing to the deletion of the δ-sarcoglycan gene.