ABCMdb

PMID: 25417047

Koo DH, Ryu MH, Ryoo BY, Beck MY, Na YS, Shin JG, Lee SS, Kim EY, Kang YK
Association of ABCG2 polymorphism with clinical efficacy of imatinib in patients with gastrointestinal stromal tumor.
Cancer Chemother Pharmacol. 2015 Jan;75(1):173-82. doi: 10.1007/s00280-014-2630-6. Epub 2014 Nov 23., [PubMed]

Sentences

No. Mutations Sentence Comment

103 ABCG2 p.Gln141Lys ABCG2 p.Gln141Lys The most studied polymorphism in ABCG2 is the non-synonymous SNP 421C>A in exon 5, which results in a glutamine to lysine substitution at codon 141 (Q141K), localized in the ATP-binding domain [24]. Login to comment 104 ABCG2 p.Gln141Lys It is well known that ABCG2 harboring the Q141K polymorphism results in impaired expression, incomplete transport to the plasma membrane, and decreased efflux function of BCRP, and consequently results in reduced clearance of ABCG2 substrate drugs [25]. Login to comment 105 ABCG2 p.Gln141Lys As cells expressing ABCG2 Q141K have a higher imatinib accumulation in vitro compared to cells wild type in ABCG2, this variant form of ABCG2 is associated with TableÊf;5ߒߙImatinib plasma trough level according to genotype SD standard deviation, BSA body surface area, Hb hemoglobin, WBC white blood cell, CCr creatinine clearance * p value for log-transformed imatinib level ** After adjusting for sex, age, BSA, Hb, Albumin, and CCr *** Patients who received imatinib for metastatic or recurrent GIST (N = 145) Genotype (N) Imatinib trough level (ng/mL) p value* p value** p value*** Mean SD CYP3A5 6986A>G AA (13) 1,342.8 450.3 0.918 0.764 0.656 AG (68) 1,375.6 633.3 GG (128) 1415.8 711.7 ABCB1 1236C>T CC (35) 1346.3 673.9 0.205 0.573 0.092 CT (94) 1347.2 678.3 TT (80) 1480.7 662.1 2677G>A/T GG (41) 1477.4 774.9 0.394 0.315 0.447 Hetero (135) 1350.2 620.5 TT (33) 1495.8 734.3 3435C>T CC (81) 1454.9 672.1 0.338 0.258 0.239 CT (98) 1343.4 708.1 TT (30) 1423.9 538.1 ABCG2 34G>A GG (119) 1360.5 486.8 0.930 0.940 0.959 GA (75) 1393.8 727.1 AA (15) 1405.7 659.2 421C>A CC (103) 1339.3 655.3 0.216 0.477 0.201 CA (88) 1477.4 693.5 AA (18) 1347.9 648.6 Fig.Êf;2ߒߙImatinib trough plasma levels according to genetic polymorphisms among metabolizer and efflux-transporter genes. Login to comment 107 ABCG2 p.Gln141Lys This impaired functioning of the ABCG2 protein in cells transfected with ABCG2 Q141K is similar to the result of SNP-induced alterations in the function of the BCRP protein itself [28]. Login to comment