ABCMdb

PMID: 15618737

Itoda M, Saito Y, Shirao K, Minami H, Ohtsu A, Yoshida T, Saijo N, Suzuki H, Sugiyama Y, Ozawa S, Sawada J
Eight novel single nucleotide polymorphisms in ABCG2/BCRP in Japanese cancer patients administered irinotacan.
Drug Metab Pharmacokinet. 2003;18(3):212-7., [PubMed]

Sentences

No. Mutations Sentence Comment

11 ABCG2 p.Phe489Leu ABCG2 p.Phe431Leu MPJ6äAG2017 and MPJ6äAG2020 resulted in amino acid alterations, F431L and F489L, respectively. Login to comment 46 ABCG2 p.Gln141Lys ABCG2 p.Val12Met ABCG2 p.Ile206Leu ABCG2 p.Asn590Tyr Information on ABCG2WBCRP single nucleotide polymorphisms (SNPs) has been published.8-10) Five naturally occurring nonsynonymous SNPs have been reported in Japanese and Caucasians: V12M, Q126Stop, Q141K, I206L, and N590Y.8-10) SNP Q126Stop was found in 3 out of 124 healthy Japanese subjects.9) Since it may be possible that ABCG2WBCRP polymorphisms are associated with the eŠectiveness and adverse eŠects of irinotecan, ABCG2WBCRP exons and their ‰anking regions were sequenced to identify Japanese speciˆc SNPs. Login to comment 98 ABCG2 p.Phe489Leu ABCG2 p.Phe431Leu Novel SNPs in the ABCG2 gene found in Japanese individuals SNP name AG2005 AG2007 AG2012 AG2015 AG2017 AG2019 AG2020 AG2023 Intron 2 Intron 3 Intron 6 Exon 9 Exon 11 Intron 11 Exon 12 Intron 13 Position (cDNA) IVS2－93a IVS3＋71ä72 insTb IVS6－204 1098 1291 IVS11－135 1465 IVS13＋65 Nucleotide TÀC -ÀT CÀT GÀA TÀC GÀA TÀC TÀG Amino acid E366E F431L F489L Frequency, z T:97.5 -:99.2 C:96.7 G:99.2 T:99.2 G:98.3 T:99.2 G:99.2 C:2.5 T:0.8 T:3.3 A:0.8 C:0.8 A:1.7 C:0.8 A:0.8 a Numbers following IVS (intervening sequence) represents number of the preceding exon. In the case of end of the intron, the SNP position is expressed by a minus sign and the bases upstream of the next exon. Login to comment 107 ABCG2 p.Phe489Leu ABCG2 p.Phe431Leu Of these SNPs, two SNPs, MPJ6äAG2017 and 020, that were each found in 1 subject, introduced nonsynonymous amino acid changes (F431L and F489L), respectively. Login to comment 108 ABCG2 p.Arg482Thr ABCG2 p.Arg482Gly Honjo et al. recently reported that R482T and R482G variants were found in cells after drug selection.11) ABCG2-ATPase activity was in‰uenced by amino acid residue 482,12) which might be located within the transmembrane domain.10) Currently, the functional signiˆcance of these SNPs is unknown; however, the clinical outcome of those who have these non-synonymous SNPs should carefully be evaluated. Login to comment 119 ABCG2 p.Phe431Leu (E) Homozygous wild-type and wild-typeW1291TÀC (F431L) (MPJ6äG2017). Login to comment 121 ABCG2 p.Phe489Leu (G) Homozygous wild-type and wild-typeW1465TÀC (F489L) (MPJ6äG2020). Login to comment 126 ABCG2 p.Gln141Lys ABCG2 p.Val12Met Masaya ITODA, et al.SNP18 (216) Novel ABCG2 SNPs SNP19 (217) tion of ABCG2WBCRP haplotypes in conjunction with other frequently found SNPs, including non-synonymous ones (34GÀA (V12M, SNP frequency 19z) and 421CÀA (Q141K, SNP frequency 33z)) in the Japanese population. Login to comment 128 ABCG2 p.Gln141Lys ABCG2 p.Val12Met MPJ6äAG2012 was closely associated with the known SNP, IVS1-99GÀA (rs1584481, ssj0001922), but not with the SNPs, 34GÀA (V12M) and 421CÀA (Q141K). Login to comment