ABCMdb

PMID: 19605531

Cotte S, von Ahsen N, Kruse N, Huber B, Winkelmann A, Zettl UK, Starck M, Konig N, Tellez N, Dorr J, Paul F, Zipp F, Luhder F, Koepsell H, Pannek H, Montalban X, Gold R, Chan A
ABC-transporter gene-polymorphisms are potential pharmacogenetic markers for mitoxantrone response in multiple sclerosis.
Brain. 2009 Sep;132(Pt 9):2517-30. Epub 2009 Jul 15., [PubMed]

Sentences

No. Mutations Sentence Comment

42 ABCG2 p.Gln141Lys ABCG2 p.Val12Met TaqManTM PCR was performed for ABCG2 V12M (reference SNP rs2231137) and Q141K (rs2231142) using Platinum qPCR SuperMix-UDG (Invitrogen, Karlsruhe, Germany) on a 7500 Real Time PCR system (Applied Biosystems, Darmstadt, Germany). Login to comment 70 ABCG2 p.Gln141Lys ABCG2 p.Val12Met Retrospective clinical correlation of genotype and MX response Patient samples were genotyped for ABCB1 2677 G4T, 3435C4T, ABCG2 V12M and Q141K and retrospectively correlated with clinical MX response. Login to comment 102 ABCG2 p.Gln141Lys ABCG2 p.Val12Met Of five different ABCG2 SNPs with potential functional significance investigated, only reference SNP (rs) 2231137 (G4A) leading to a V12M substitution and rs2231142 (C4A) resulting in a Q141K substitution were observed. Login to comment 110 ABCG2 p.Gln141Lys ABCG2 p.Val12Met A high degree of linkage disequilibrium was found between ABCG2 V12M and Q141K [linkage D` = 0.854, (Gaunt et al., 2007)]. Login to comment 207 ABCG2 p.Gln141Lys ABCG2 p.Gln141Lys ABCG2 p.Val12Met ABCG2 p.Val12Met For ABCG2, only V12M and Q141K polymorphisms could be detected, in vitro leading to disruption of apical membrane localization (V12M) or decreased ATPase function (Q141K) Table 3 Association of ABC-transporter genotype with therapeutic response to MX monotherapy, exact Cochran-Armitage test (P = 0.039) (panel A), or MX/GC combination therapy (P = 0.348) (panel B) Total, n (%) Responder, n (%) Non-Responder, n (%) A: MX monotherapy ABCB1/ABCG2-H 24 (15.5) 15 (62.5) 9 (37.5) ABCB1/ABCG2-I 98 (63.2) 78 (79.6) 20 (20.4) ABCB1/ABCG2-L 33 (21.3) 28 (84.8) 5 (15.2) Total 155 121 (78.1) 34 (21.9) B: MX/GC combination therapy ABCB1/ABCG2-H 21 (13.6) 12 (57.1) 9 (42.9) ABCB1/ABCG2-I 100 (64.9) 58 (58.0) 42 (42.0) ABCB1/ABCG2-L 33 (21.4) 21 (63.6) 12 (36.4) Total 154 91 (59.1) 63 (40.9) Retrospective analysis using EDSS, relapse rate and MSFC as main outcome parameters to define responders and non-responders, respectively. Login to comment