ABCMdb

ABCC2 p.Met233Ile

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Publications

PMID: 22695893 [PubMed] Endo S et al: "Association study of genetic polymorphisms of drug transporters, SLCO1B1, SLCO1B3 and ABCC2, in African-Americans, Hispanics and Caucasians and olmesartan exposure."

No. Sentence Comment

11 At least three nonsynonymous SNPs have been found so far, with 334T4G (S112A) and 699G4A (M233I) increasing transporter activity in vitro.11 With regard to ABCC2, several mutations and deletions have been identified in patients with Dubin-Johnson syndrome, an autosomal recessive disorder, each of which impairs either the expression or function of MRP2 protein.12-14 Beside mutations in Dubin-Johnson syndrome, the extensive genetic variation identified so far may have a potential effect on drug disposition.15,16 In fact, the T allele of À24C4T has been 1Translational Medicine and Clinical Pharmacology Department, Daiichi Sankyo, Tokyo, Japan; 2Discovery Science and Technology Department, Daiichi Sankyo RD Novare, Tokyo, Japan; 3Translational Medicine and Clinical Pharmacology Department, Daiichi Sankyo Pharma Development, Edison, NJ, USA; 4Department of Clinical Pharmacokinetics, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan and 5Department of Molecular Pharmacokinetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan Correspondence: Dr I Ieiri, Kyushu University, Clinical Pharmacokinetics, 3-1-1, Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. Login to comment
125 However, interestingly, there were 32 SNPs that showed a high LD (r240.8 in all populations) relationship with SNP 693, including the cSNPs at 683 (334T4G, S112A, rs4149117 in exon 4), 721 (699G4A, M233I, rs7311358 in exon 7) and 757 (1557A4G, A519A, rs2053098 in exon 12) (data not shown). Login to comment