ABCB4 p.Val135Ile
| Predicted by SNAP2: | A: N (61%), C: N (72%), D: D (71%), E: D (66%), F: D (59%), G: D (53%), H: D (53%), I: N (93%), K: D (71%), L: D (63%), M: N (57%), N: D (59%), P: D (80%), Q: D (59%), R: D (66%), S: N (53%), T: N (61%), W: D (75%), Y: D (59%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: D, G: D, H: D, I: N, K: D, L: N, M: N, N: D, P: D, Q: D, R: D, S: D, T: D, W: D, Y: D, |
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[hide] Three hundred twenty-six genetic variations in gen... J Hum Genet. 2002;47(1):38-50. Saito S, Iida A, Sekine A, Miura Y, Ogawa C, Kawauchi S, Higuchi S, Nakamura Y
Three hundred twenty-six genetic variations in genes encoding nine members of ATP-binding cassette, subfamily B (ABCB/MDR/TAP), in the Japanese population.
J Hum Genet. 2002;47(1):38-50., [PMID:11829140]
Abstract [show]
We screened DNAs from 48 Japanese individuals for single-nucleotide polymorphisms (SNPs) in nine genes encoding components of ATP-binding cassette subfamily B (ABCB/MDR/TAP) by directly sequencing the entire applicable genomic regions except for repetitive elements. This approach identified 297 SNPs and 29 insertion/deletion polymorphisms among the nine genes. Of the 297 SNPs, 50 were identified in the ABCB1 gene, 14 in TAP], 35 in TAP2, 48 in ABCB4, 13 in ABCB7, 21 in ABCB8, 21 in ABCB9, 13 in ABCB10, and 82 in ABCB11. Thirteen were located in 5' flanking regions, 237 in introns, 37 in exons, and 10 in 3' flanking regions. These variants may contribute to investigations of possible correlations between genotypes and disease-susceptibility phenotypes or responsiveness to drug therapy.
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No. Sentence Comment
66 However, we detected four novel nonsynonymous polymorphisms (Val135Ile in ABCB8, Val121Met in ABCB9, Ala150Ser in ABCB10, and Val444Ala in ABCB11).
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ABCB4 p.Val135Ile 11829140:66:61
status: NEW35 Accession numbers of the genomic sequences obtained for this study are as follows: ABCB1 (AC002457.1, AC005068.1) TAP1 (X66401.1) TAP2 (X66401.1) ABCB4 (AC079591.1, AC079303.3, AC005045.2) ABCB7 (AL360179.3, AC002417.1) ABCB8 (AC010973.4) ABCB9 (AC026362.9, AC073857.10) ABCB10 (AL121990.9) ABCB11 (AC008177.3, AC069137.3) Table 1D. Summary of genetic variations detected in the ABCB4 gene No. Location Positiona Genetic variation NCBI SNP ID 1 Exon 3 3 C/T(5ЈUTR) 2 Intron 3 45 T/C 3 Intron 3 498 C/T 4 Intron 3 515 A/G 5 Intron 6 1030 G/C 6 Intron 6 1437 G/A 7 Intron 6 2449 G/A 8 Intron 7 451 A/C 9 Intron 7 530 C/G 10 Intron 7 -1023 A/G rs988448 11 Intron 7 -152 T/C 12 Exon 8 40 C/T(Leu59Leu) 13 Intron 8 130 T/C 14 Intron 8 248 A/G 15 Intron 8 531 A/G 16 Intron 8 4240 T/A 17 Intron 8 4343 C/T 18 Intron 8 4677 G/C 19 Intron 9 113 A/G 20 Intron 9 982 T/A 21 Exon 10 160 C/T(Asn168Asn) rs1202283 22 Intron 10 218 T/C rs1473154 23 Intron 11 241 A/G 24 Intron 11 457 A/G 25 Intron 11 589 T/G rs1473152 26 Intron 11 1337 C/G 27 Exon 12 3 A/T(Ile237Ile) 28 Intron 12 1288 T/C 29 Intron 12 2697 G/T rs1014283 30 Intron 13 206 G/A 31 Intron 13 988 T/C 32 Intron 13 1386 A/G rs1468615 33 Intron 13 1413-1414 T/ins 34 Intron 13 1931 A/G 35 Intron 14 402 A/C rs1149222 36 Intron 18 519 G/A rs31674 37 Intron 20 1819 C/T rs31669 38 Intron 21 16 T/C rs31668 39 Intron 21 72 C/T rs31667 40 Intron 22 767 A/del 41 Intron 23 784 T/C 42 Intron 25 158 T/C 43 Intron 25 1044 C/T rs31662 44 Intron 25 2920 T/A 45 Intron 27 580 A/G rs31659 46 Intron 27 2068 G/A rs31658 47 Intron 29 411 A/C 48 Intron 30 2991 C/T rs31653 49 Intron 31 642 C/T rs1526090 50 3Ј Flanking 458 T/C ABCB4, ATP-binding cassette, subfamily B, member 4 Accession numbers of the mRNA sequences are as follows: ABCB1 (M14758.1) TAP1 (NM_000593.2) TAP2 (XM_039609.1) ABCB4 (NM_000443.2) ABCB7 (AF038950.1) ABCB8 (NM_007188.2) ABCB9 (AF216494.1) ABCB10 (NM_012089.1) ABCB11 (NM_003742.1) Table 1E. Summary of genetic variations detected in the ABCB7 gene No. Location Position Genetic variation NCBI SNP ID 1 Intron 1 220 C/A 2 Intron 1 480 G/A 3 Intron 1 512-513 AT/del 4 Intron 1 1690 G/A 5 Intron 1 5309 G/A 6 Intron 1 -11274 A/G 7 Intron 1 -11085 A/G 8 Intron 1 -10037 T/C 9 Intron 1 -21 G/A 10 Intron 3 135-136 A/ins 11 Intron 3 333 G/A 12 Intron 12 524 C/T 13 Intron 13 1543 G/A 14 Intron 13 2400 C/G 15 Intron 15 2201 G/C ABCB7, ATP-binding cassette, subfamily B, member 7 Table 1F. Summary of genetic variations detected in the ABCB8 gene No. Location Position Genetic variation NCBI SNP ID 1 5Ј Flanking -2272 T/C 2 5Ј Flanking -2070 G/A 3 Intron 1 25 A/C 4 Exon 2 308 G/A(Val135Ile) 5 Intron 2 334 C/G 6 Intron 4 12 C/T 7 Intron 5 547 G/A 8 Exon 7 57 A/T(Arg328Arg) 9 Intron 9 1231 C/T 10 Intron 9 1245 G/A rs1469549 11 Intron 9 2164 C/T 12 Intron 9 2645 C/del 13 Intron 9 2646 G/A 14 Intron 9 3229 G/A 15 Intron 12 113-114 GG/ins 16 Intron 13 128 C/T 17 Intron 13 305 A/G 18 Intron 14 135 C/G 19 Intron 14 159 A/T 20 Intron 15 747 A/G 21 3Ј Flanking 48 C/A rs891506 22 3Ј Flanking 333 G/A 23 3Ј Flanking 1168 G/A 24 3Ј Flanking 1719-1721 GTC/del ABCB8, ATP-binding cassette, subfamily B, member 8 Amplification of samples and detection of polymorphisms Total genomic DNAs were isolated from peripheral leukocytes of 48 unrelated Japanese individuals by the standard phenol/chloroform extraction method.
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ABCB4 p.Val135Ile 11829140:35:2664
status: NEW[hide] Pharmacogenetics of target genes across doxorubici... Curr Drug Metab. 2010 Jan;11(1):115-28. Lal S, Mahajan A, Chen WN, Chowbay B
Pharmacogenetics of target genes across doxorubicin disposition pathway: a review.
Curr Drug Metab. 2010 Jan;11(1):115-28., [PMID:20302569]
Abstract [show]
Increased understanding of the molecular mechanisms of tumor heterogeneity combined with rapid advances in the field of pharmacogenetics and pharmacogenomics have fuelled studies on individualizing anticancer therapy. Doxorubicin (Adriamycin), is an anthracycline glycoside antibiotic originally produced by Streptomyces peucetius var. caesius, and is widely used either as a single agent or in combination with other chemotherapeutic regimens for curative, adjuvant, and palliative treatment in cancer patients. The pharmacogenetics of doxorubicin has not been well characterized. The polygenic influence of functional candidate gene variants across doxorubicin biochemical pathway is hypothesized to contribute to its heterogeneity in disposition, influencing the efficacy of treatment and occurrence of adverse effects like cardiomyopathy in patients undergoing doxorubicin based adjuvant and neo-adjuvant chemotherapy. The pharmacogenetics of Asian population differs from that of other ethnic groups, particularly from Caucasian and African populations, and indicates an important role of ethnicity in determining predictive end points during chemotherapy and in individualizing treatment. This review comprehensively examines the pharmacogenetics of the regulatory nuclear receptor Pregnane-X Receptor (PXR), influx (SLC22A16) and efflux drug transporters (ABCB1, ABCG2, ABCC5, ABCB5 and RLIP76) and drug metabolizing enzymes (CBR1, CBR3) across the biochemical pathway of doxorubicin in Asian breast cancer patients receiving doxorubicin based adjuvant chemotherapy. The influence of functional genetic variants on the inter-individual variability in pharmacokinetics of doxorubicin and its major metabolite are also discussed. The incorporation of non-genetic factors and subsequent validation of these findings in different patient and population groups will be valuable in tailoring doxorubicin dosage regimens to an individual to maximize therapeutic efficacy and minimize adverse reactions, leading to improved clinical outcomes.
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135 Among the 8 exonic SNPs found, six result in non-synonymous transitions: 148C>T (p.R50W), c.403G>A (p.V135I), c.910C>T (p.R304C), c.1624G>A (p.V542I), c.1679C>G (p.S560C) and c.2129G>A (p.G710V).
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ABCB4 p.Val135Ile 20302569:135:102
status: NEW