Title:
Pharmacogenomic information (SNPs and miRNA monitoring) for individualized drug therapy and drug development
※ 日本語での講演（ The seminar will be given in Japanese.)

Ichiro Ieiri
Department of Clinical Pharmacokinetics, Graduate School of Pharmaceutical Sciences, Kyushu University

Abstract:
Interindividual differences in breast cancer resistance protein (BCRP, ABCG2 ) function were evaluated from the viewpoints of genetic polymorphisms and miRNA levels in plasma. The miRNA-328 expression levels were negatively correlated with BCRP mRNA levels as well as protein levels in human placental samples. Since large interindividual differences were observed in placental miRNA-328 levels, we analyzed CpG methylation status of regions upstream pre-miR328. Results indicate that the methylation status at some CpG islands play an important role for placental BCRP expression. To explore these observations into the clinical application, the utility of miR-328 monitoring in plasma was evaluated. Plasma miR-328 levels were significantly correlated with AUC values of sulfasalazine (a good in vivo probe for intestinal BCRP function), suggesting that the plasma miR-328 level is a good bio-marker for intestinal BCRP function.

References:
Functional assessment of ABCG2 (BCRP) gene polymorphisms to protein expression in human placenta. Drug Metab Dispos . 2005 33:94-101.

Pharmacogenetic characterization of sulfasalazine disposition based on NAT2 and ABCG2 ( BCRP ) gene polymorphisms in humans. Clin Pharmacol Ther . 2008 84:95-103.