PMID: 19005482

Rocha V, Porcher R, Fernandes JF, Filion A, Bittencourt H, Silva W Jr, Vilela G, Zanette DL, Ferry C, Larghero J, Devergie A, Ribaud P, Skvortsova Y, Tamouza R, Gluckman E, Socie G, Zago MA
Association of drug metabolism gene polymorphisms with toxicities, graft-versus-host disease and survival after HLA-identical sibling hematopoietic stem cell transplantation for patients with leukemia.
Leukemia. 2009 Mar;23(3):545-56. Epub 2008 Nov 13., [PubMed]
Sentences
No. Mutations Sentence Comment
14 ABCB1 p.Ala313Gly
X
ABCB1 p.Ala313Gly 19005482:14:297
status: NEW
view ABCB1 p.Ala313Gly details
 Samples of 107 leukemia patients given HLA-identical HSCT and their respective donors were analyzed for the following candidate genes polymorphisms: P450 cytochrome family [CYP2B6*2(C64T), *3(C777A), *4(A785G), *5(C1459T), *6(G516T)] glutathione-S-transferases [GSTM1 (null), GSTT1 (null), GSTP1 (A313G)], Multidrug-resistance gene [MDR1 (C3435T)], Methylenetetrahydrofolate reductase [MTHFR (C677T, A1298C)], Vitamin D receptor [VDR (ApaI, TaqI and BsmI)]. Login to comment 53 ABCB1 p.Ala313Gly
X
ABCB1 p.Ala313Gly 19005482:53:1127
status: NEW
view ABCB1 p.Ala313Gly details
 However, both Table 2 Characteristics of genes and polymorphisms Allele polymorphisms Primers PCR 35 cycles Fragment enzyme References CYP2B6*2 50 -GCAGGGCAGTCAGACCAGGA-30 30 s 94 1C 215 bp 13 C64T 50 -GACCCCATTCGTCTGTGTCT-30 40 s 58 1C (Modified) Arg22 Cys 1 min 72 1C Hae II CYP2B6*3 50 -CACCACCCCTTCTTTCTTGC-30 30 s 94 1C 223 bp 14 C777A 50 -CCTTTTTCCTCTCCCAGACC-30 40 s 58 1C Ser259 Arg 1 min 72 1C Hae II CYP2B6*4 50 -GACAGAAGGATGAGGGAGGAA-30 30 s 94 1C 640 bp 13 A785G 50 -CTCCCTCTGTCTTTCATTGTGT-30 45 s 60 1C Lys262 Arg 1 min 72 1C StyI CYP2B6*5 50 -TGAGAATCAGTGGAAGCCATAGA-30 30 s 94 1C 1401 bp 13 C1459T 50 -TAATTTTCGATAATCTCACTCCTGC-30 40 s 58 1C Arg487 Cys 1 min 72 1C Bgl II CYP2B6*6 50 -CTTGACCTGCTGCTTCTTCC-30 30 s 94 1C 204 bp 14 G516T 50 -TCCCTCTCCGTCTCCCTG-30 40 s 58 1C Gln172 His 1 min 72 1C Bsr I GSTM1 50 -GAACTCCCTGAAAAGCTAAAGC-30 1 min 94 1C 215 bp 15 Present or null 50 -GTTGGGCTCAAATATACGGTGG-30 1 min 62 1C 1 min 72 1C GSTT1 50 -TTCCTTACTGGTCCTCACATCTC-30 1 min 94 1C 480 bp 15 Present or null 50 -TCACCGGATCATGGCCAGCA-30 1 min 62 1C 1 min 72 1C GSTP1 50 -ATCCCCAGTGACTGTGTGTT-30 30 s 94 1C 217 bp 16 A313G 50 -CTTTCTTTGTTCAGCCCCCA-30 40 s 53 1C (Modified) Ile105 Val 1 min 72 1C BsmAI MDR 50 - GATCTGTGAACTCTTGTTTTCA-30 30 s 94 1C 244 bp 17 C3435T 50 -GAAGAGAGACTTACATTAGGC-30 45 s 62 1C synonymous 1 min 72 1C Dpn II MTHFR 50 -AGGCGGTGCGGTGAGAGTG-30 50 s 94 1C 198 bp 18 C677T 50 -TGAAGGAGAAGGTGTCTGCGG GA-30 50 s 56 1C Ala222 Val 1 min 72 1C Hinf I MTHFR 50 -CTTTGGGGAGCTGAAGGACTACTAC-30 1 min 92 1C 163 bp 19 A1298C 50 -CAGTTTGTGACCATTCCGGTTTG-30 1 min 51 1C Glu429 Ala 30 s 72 1C Mbo II For each allele, the nucleotide and amino acid changes are indicated (when appropriate), together with the primer sequences, PCR conditions (35 cycles for all the amplification protocols), size of the fragment amplified and the restriction enzyme. Login to comment 61 ABCB1 p.Ala313Gly
X
ABCB1 p.Ala313Gly 19005482:61:977
status: NEW
view ABCB1 p.Ala313Gly details
 of donors (%) CYP2B6*2A Cyclophosphamide CC (wt) Not described 92 (86) 91 (85) C64T CT 14 (13) 15 (14) TT 1 (1) 1 (1) CYP2B6*4 AA (wt) AG or GG trend to lower expression of the enzyme13 59 (55) 60 (56) A785G AG 38 (36) 37 (35) GG 10 (9) 10 (9) CYP2B6*5 CC (wt) CT or TT Significantly lower S-mephentytoin N-demethylase activity13 81 (76) 89 (83) C1459T CT 25 (23) 16 (15) TT 1 (1) 2 (2) CYP2B6*6 GG (wt) GT or TT decreased protein level and impact on CY 4-hydroxylation.8 Enhance 7-ethoxycoumarin O-deethylase activity14 61 (57) 63 (59) G516T1 GT 36 (34) 35 (33) A785G TT 10 (9) 9 (9) GSTM1* Null Reduced or no enzyme activity and therefore may be unable to eliminate electrophilic carcinogens24 61 (57) 60 (56) Busulfan Non-null 46 (43) 47 (44) GSTT1* Melphalan Null 20 (19) 27 (25) Cyclophosphamide Non-null 87 (81) 80 (75) GSTP1 AA (wt) Reduced ability to detoxify chemotherapeutic agents thereby increasing the effective dose of the drug within the cell.25 46 (43) 52 (49) A313G GA 53 (49) 42 (39) GG 8 (8) 13 (12) MTHFR Methotrexate CC (wt) It leads to a thermolabile variant of the enzyme and it is associated with reduced enzyme activity (70% for TT and 40% for CT), increased homocysteine levels18 45 (42) 41 (38) C677T CT 53 (50) 51 (48) TT 9 (8) 15 (14) MTHFR AA (wt) Reduced enzyme activity without increasing homocysteine levels.26 50 (47) ND A1298C AC 56 (52) ND CC 1 (1) ND MDR-1 Cyclosporine A C3435T Tracolimus CC (wt) CsA oral clearance is significantly higher in subjects who carried at least one T allele27 30 (28) 29 (27) CT 56 (52) 56 (52) TT 21 (20) 22 (21) VDR apaI aa Increased femoral and vertebral bone density.28 25 (23) 20 (19) Aa 57 (53) 56 (52) AA 25 (23) 31 (29) VDR taqI Cyclosporine A** tt Intervertebral disc degeneration in males29 Periodontal disease30 and infections31 13 (12) 15 (14) Tt 46 (43) 52 (49) Immunoregulatory activities of 1a,25-(OH)2D3 TT 48 (45) 40 (37) VDR bsmI bb Increased femoral and vertebral bone density.28 50 (47) 40 (37) Bb 34 (32) 41 (38) BB 23 (21) 26 (24) Abbreviations: ND, not done; wt, wild type. Login to comment 105 ABCB1 p.Ala313Gly
X
ABCB1 p.Ala313Gly 19005482:105:50
status: NEW
view ABCB1 p.Ala313Gly details
 In univariate analysis we found that donor GSTP1 (A313G) genotype (GG or GA) was associated with higher incidence of chronic GvHD. Login to comment