Pharmacogenomics of Human ABC Transporters: Detection of Clinically Important SNPs by SmartAmp2 Method

Wanping      Aw; Ikuko      Ota; Yu      Toyoda; Alexander      Lezhava; Yasuo      Sakai; Tsuneaki      Gomi; Yoshihide      Hayashizaki; Toshihisa      Ishikawa

Abstract

Genetic polymorphisms and mutations in drug metabolizing enzymes, transporters, receptors, and other drug targets (e.g., toxicity targets) are linked to inter-individual differences in the efficacy and toxicity of many medications as well as risk of genetic diseases. Validation of clinically important genetic polymorphisms and the development of new technologies to rapidly detect clinically important variants are critical issues for advancing personalized medicine. A key requirement for the advancing personalized medicine resides in the ability of rapidly and conveniently testing patients genetic polymorphisms and/or mutations. We have recently developed a rapid and cost-effective method, named Smart Amplification Process 2 (SmartAmp2), which enables us to detect genetic polymorphisms or mutations in target genes within 30 to 45 min under isothermal conditions without DNA isolation and PCR amplification. Detection of mutations or single nucleotide polymorphisms (SNPs) in human ABC transporter genes is becoming more important, since their functional impairments are reportedly associated with inherited diseases. Thus, certain genetic polymorphisms of ABC transporters are considered important biomarkers for diagnosis of inherited diseases and/or risk of drug-induced adverse reactions. In this review article, we will present the new technology of the SmartAmp2 method and its clinical applications for detection of SNPs in human ABC transporter genes, i.e., ABCC4 and ABCC11.

Keywords: ABCC4 (MRP4), ABCC11 (MRP8), apocrine gland, breast cancer, osmidrosis, thiopurine S-methyltransferase (TPMT), S-methyltransferase (TPMT), Genetic polymorphisms, drug targets, Smart Amplification Process 2, PCR amplification, Allele-Specific PCR, MS analysis, SNPs