ABCMdb

PMID: 12359865

Schwab M, Eichelbaum M, Fromm MF
Genetic polymorphisms of the human MDR1 drug transporter.
Annu Rev Pharmacol Toxicol. 2003;43:285-307. Epub 2002 Jan 10., [PubMed]

Sentences

No. Mutations Sentence Comment

50 ABCB1 p.Ser400Asn ABCB1 p.Asn21Asp ABCB1 p.Phe103Leu Of the 15 identified SNPs, three polymorphisms resulted in protein alterations, one in exon 2 (Asn21Asp), in exon 5 (Phe103Leu), and in exon 11 (Ser400Asn). Login to comment 52 ABCB1 p.Asn21Asp ABCD1 p.Ala61Gly The SNPs at positions A61G (Asn21Asp), C1236T, and C3435T had been reported previously (23, 26). Login to comment 54 ABCB1 p.Asn183Ser ABCB1 p.Asn183Ser ABCB1 p.Ser1141Thr ABCB1 p.Ser1141Thr ABCB1 p.Arg492Cys ABCB1 p.Arg492Cys Further SNPs of the MDR1 gene were identified in Asians, an A to G transversion 41 bases upstream from the initial position of exon 1a (A-41aG) and a C to G transversion at -145 in exon 1a (C-145G) (28), as well as three nonsynonymous mutations A548G (Asn183Ser), C1474T (Arg492Cys), and T3421A (Ser1141Thr) in different ethnic populations (29, 30). Login to comment 58 ABCB1 p.Thr1236Cys Thus, a cosegregation of the silent mutation 3435T in 62% with the T allele of the nonsynonymous exon 21 SNP 2677T and the T allele of the synonymous exon 12 polymorphism T1236C was reported for European Americans (29). Login to comment 60 ABCC1 p.Ala893Ser ABCC1 p.Ala893Thr ABCB1 p.Asn183Ser ABCB1 p.Ser400Asn ABCB1 p.Asn21Asp ABCB1 p.Gln1107Pro ABCB1 p.Phe103Leu ABCB1 p.Ala999Thr ABCB1 p.Ser1141Thr ABCB1 p.Arg492Cys ABCB1 p.Met986Val In a Northern Italian population, the extent of linkage disequilibrium TABLE 2 Summary of MDR1 genetic variants in different ethnic groups Location Position Allele Effect Reference promotor 5 flanking/-41a A (28) G exon 1a exon 1a/-145 C (28) G exon 1b exon 1b/-129 T (25, 33) C intron 1 exon 2/-4 C (29) T intron 1 exon 2/-1 G initiation of translation (25, 27, 29) A exon 2 exon 2/61 A Asn21Asp (25-27, 29) G intron 4 exon 5/-35 G (25) C intron 4 exon 5/-25 G (25) T exon 5 exon 5/307 T Phe103Leu (25) C intron 6 exon 6/+139 C (25, 27) T intron 6 exon 6/+145 C (25) T exon 7 exon 7/548 A Asn183Ser (29) G exon 11 exon 11/1199 G Ser400Asn (25, 27, 29) A exon 12 exon 12/1236 C wobble (23, 25, 27, 29) T (Gly412Gly) intron 12 exon 12/+44 C (25, 27) T exon 13 exon 13/1474 C Arg492Cys (29) T intron 16 exon 17/-76 T (25, 27) A intron 17 exon 17/137 A (25) G exon 21 exon 21/2650 C wobble (29) T (Leu884Leu) (Continued ) TABLE 2 (Continued) Location Position Allele Effect Reference exon 21 exon 21/2677 G (22, 23, 27, 29) T Ala893Ser A Ala893Thr exon 24 exon 24/2956 A Met986Val (33) G exon 24 exon 24/2995 G Ala999Thr (22) A exon 26 exon 26/3320 A Gln1107Pro (27) C exon 26 exon 26/3396 C wobble (25) T exon 26 exon 26/3421 T Ser1141Thr (29, 30) A exon 26 exon 26/3435 C wobble (23, 25, 29) T (Ile1145Ile) exon 28 exon 28/4030 G (33) C exon 28 exon 28/4036 A (23, 33) G The positions of the polymorphisms correspond to positions of MDR1 cDNA with the first base of the ATG start codon set to 1 (GenBank accession # M14758). Login to comment 68 ABCB1 p.Asn21Asp ABCD1 p.Ala61Gly The A61G mutation (Asn21Asp) results in a net charge change (basic to acidic) close to the N-terminus of P-glycoprotein, which appears to be of minor functional importance if recombinant mutational analyses of P-glycoprotein are considered (6). Login to comment 69 ABCB1 p.Phe103Leu The protein alteration Phe103Leu in exon 5 is located next to the second transmembrane domain on the extracellular side of P-glycoprotein and is in close vinicity to glycosylation sites of P-glycoprotein. Login to comment 71 ABCB1 p.Ser400Asn The nonsynonymous G1199A SNP in exon 11 (Ser400Asn) results in a significant size change dependent on pH and isoelectric environment of the residue, leading possibly to a charge change in the protein. Login to comment 73 ABCC1 p.Ala893Ser ABCB1 p.Ala999Thr Both polymorphisms, G2677T/A and G2995A, resulting in amino acid exchanges in exon 21 (Ala893Ser/Thr) and exon 24 (Ala999Thr), respectively, are located in the second transmembrane domain, the exon G2995A polymorphism closer to the ABC domain. Login to comment 86 ABCC1 p.Ala893Ser ABCB1 p.Ser400Asn ABCB1 p.Asn21Asp ABCB1 p.Phe103Leu ABCB1 p.Ala999Thr However, a recent publication characterized the functional consequences of five coding SNPs (Asn21Asp, Phe103Leu, Ser400Asn, Ala893Ser, Ala999Thr) using a vaccinia virus-based transient expression system (40a). Login to comment 312 ABCB1 p.Asn21Asp A new polymorphism (N21D) in the exon 2 of the human MDR1 gene encoding the P-glycoprotein. Login to comment