ABCMdb

PMID: 16788565

Haenisch S, Zimmermann U, Dazert E, Wruck CJ, Dazert P, Siegmund W, Kroemer HK, Warzok RW, Cascorbi I
Influence of polymorphisms of ABCB1 and ABCC2 on mRNA and protein expression in normal and cancerous kidney cortex.
Pharmacogenomics J. 2007 Feb;7(1):56-65. Epub 2006 Jun 20., [PubMed]

Sentences

No. Mutations Sentence Comment

4 ABCC2 p.Val417Ile The DNA of all patients was genotyped for ABCB1 À2352G4A, À692T4C, 2677G4T/A (Ala893Ser/Thr), and 3435C4T, and ABCC2 À24C4T, 1249G4A (Val417Ile) and 3972C4T. Login to comment 26 ABCC2 p.Val417Ile Cancerous and adjacent non-cancerous tissue of each patient and blood samples of controls were genotyped for the ABCB1 polymorphisms À2352G4A, À692T4C, 2677G4T/A (Ala893Ser/Thr), 3435C4T (silent), and for À24C4T, 1249G4A (Val417Ile) and 3972C4T (silent) in the ABCC2 gene. Login to comment 52 ABCB1 p.Gly1249Ala The wild-type (ABCC2-C) and the variant (ABCC2-T) fragment were ligated into the pGL3 basic vector (Promega, Mannheim, Germany) being in-frame of the translation Table 1 Primers and restriction endonucleases used for genotyping of novel ABCB1 (MDR1) and ABCC2 (MRP2) variants and primers and fluorescent probes used for cDNA real-time quantification Gene SNP Name of primer Primer sequence Restriction enzyme Fragment length (bp) mut/wt ABCB1 T-692C MDR1-692f 50 -CTA GAG AGG TGC AAC GGA AAG MspA1I 32 117 208 MDR1-692r 50 -TAG TAG CTC CCA GCT TTG CG 117 240 G-2352A MDR1-2352f 50 -TTT ACC TGA TGC TCA AGA TTG TAG MboI 179 MDR1 -2352r* 50 - TCA CTT TTG TTT TGC TTT GTT GCT TGA T 144 35 ABCB1 mdr1 forward 50 -TTC GCA ACC CCA AGA TCC TC mdr1 reverse 50 -ACA ATG GTG GTC CGA CCT TT Probe 50 -6FAM-ATC CAG AGC CAC CTG AAC CAC TGC T XT p ABCC2 C-24T MRP2-Pro 50 -TAA ATG GTT GGG ATG AAA GG BbsI 301 MRP2-ProR2 50 -GCT TTA GAC CAA TTG CAC ATC 188 113 G1249A MRP2-10* 50 -AAC TTG GCC AGG AAG GAG TAC AAC AclI 260 MRP2-10R 50 -CTG GGT GAC TTT TTC TTT ACC TGA ATG 236 24 C3972T MRP2-28 50 -AAC TTA CTT CTC ATC TTG TCT CCT TGC BsrDI 156 28 MRP2-28R* 50 -CTC CAC CTA CCT TCT CCA TGC TAG 184 ABCC2 mrp2 forward 50 -CTG GGA ACA TGA TTC GGA AGC mrp2 reverse 50 -GAG GAT TTC CCA GAG CCG AC Probe 50 -6FAM-CAG TCC GAG ATG TGA ACC TGG ACA T XT p Abbreviations: MDR1, multidrug resistance protein 1; MRP2, multidrug resistance-associated protein. Login to comment 94 ABCC2 p.Val417Ile Analyzing the ABCC2 SNPs À24C4T, 1249G4A (Val417Ile) and 3972C4T, a lower frequency of the 1249A variant, coding for isoleucin, was found in clear-cell carcinomas (15.1 vs 22.2%), however without reaching statistical significance (P ¼ 0.09). Login to comment 103 ABCB1 p.Gly1249Ala The difference, however, was statistically not significant (P ¼ 0.134), but there were increased mRNA expression levels among ABCB1 H1/H4 (P ¼ 0.044) and ABCB1 H2/H4 (P ¼ 0.01) (Mann-Whitney Table 2 Allele frequencies and frequencies of genotypes in 82 patients and in 164 controls Location Allele Allele frequency Genotype Frequency of genotypes Odds ratio P-value RCC Controls RCC controls 95% CI MDR1 G 99.4 99.1 GG 98.8 98.2 0.66 (0.03-7.29) 0.72 G-2352A A 0.6 0.9 GA 1.2 1.8 AA 0.0 0.0 T-692C T 98.0 97.0 TT 96.3 93.3 0.53 (0.11-2.12) 0.33 C 2.0 3.0 TC 3.7 6.7 CC 0.0 0.0 G2677T/A G 58.5 54.3 GG 35.4 32.3 0.87 (0.48-1.59) 0.63 T 39.6 43.6 GT 42.7 41.5 A 1.8 2.1 TT 18.3 22.0 GA 3.7 2.4 TA 0.0 1.8 AA 0.0 0.0 C3435T C 42.7 46.3 CC 18.3 22.6 1.3 (0.64-2.69) 0.44 T 57.3 53.7 CT 48.8 47.6 TT 32.9 29.9 MRP2 C 78 81.4 CC 64.6 68.9 1.21 (0.67-2.20) 0.50 C-24T T 22 18.6 CT 26.8 25.0 TT 8.5 6.1 G1249A G 83.5 77.8 GG 67.1 61.6 0.79 (0.43-1.43) 0.40 A 16.5 22.2 GA 32.9 32.3 AA 0.0 6.1 C3972T C 62.8 69.2 CC 41.5 51.2 1.48 (0.84-2.62) 0.15 T 37.2 30.8 CT 42.7 36.0 TT 15.9 12.8 Abbreviations: MDR1, multidrug resistance protein 1; MRP2, multidrug resistance-associated protein; RCC, renal cell carcinoma. Login to comment 121 ABCB1 p.Gly1249Ala Table 3 Frequencies of ABCB1 and ABCC2 haplotypes in RCC patients and controls estimated with the EH program26 ABCB1 haplotype G2677T/ A C3435T Frequency RCC Controls 1 G C 40.9 38.8 2 G T 17.7 15.5 3 T C 0.0 6.1 4 T T 39.6 37.5 5 A C 1.8 1.5 6 A T 0.0 0.6 w2 ¼ 11.63, d.f. ¼ 5, P ¼ 0.04 ABCC2 haplotype C-24T G1249A C3972T Frequency RCC Controls 1 C G C 45.8 47.0 2 T G C 0.0 1.4 3 C A C 16.4 20.8 4 T A C 0.0 0.0 5 C G T 15.8 12.2 6 T G T 22.0 17.2 7 C A T 0.0 1.4 8 T A T 0.0 0.0 w2 ¼ 8.55, d.f. ¼ 5, P ¼ 0.128 Twelve square w2 test was conducted to compare differences between haplotype frequencies of RCC and controls. Login to comment 139 ABCC2 p.Arg768Trp ABCC2 p.Ser789Phe ABCC2 p.Ala1450Thr The earlier described ABCC2 SNPs, namely 2302C4T (Arg768Trp), 2366C4T (Ser789Phe) and 4348G4A (Ala1450Thr),43 could not be found in our Caucasian volunteers (data not shown). Login to comment