ABCC4 p.His172Gln
| Predicted by SNAP2: | A: N (87%), C: N (87%), D: N (61%), E: N (61%), F: D (66%), G: N (87%), I: N (61%), K: N (66%), L: N (66%), M: N (57%), N: N (87%), P: D (53%), Q: N (78%), R: N (66%), S: N (97%), T: N (97%), V: N (78%), W: N (57%), Y: D (63%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: D, G: D, I: D, K: D, L: D, M: D, N: D, P: D, Q: D, R: D, S: D, T: D, V: D, W: D, Y: D, |
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[hide] Association study of genetic polymorphism in ABCC4... J Hum Genet. 2009 Oct;54(10):564-71. Epub 2009 Aug 21. Low SK, Kiyotani K, Mushiroda T, Daigo Y, Nakamura Y, Zembutsu H
Association study of genetic polymorphism in ABCC4 with cyclophosphamide-induced adverse drug reactions in breast cancer patients.
J Hum Genet. 2009 Oct;54(10):564-71. Epub 2009 Aug 21., [PMID:19696793]
Abstract [show]
Cyclophosphamide (CPA)-based combination treatment has known to be effective for breast cancer, but often causes adverse drug reactions (ADRs). Hence, the identification of patients at risk for toxicity by CPA is clinically significant. In this study, a stepwise case-control association study was conducted using 403 patients with breast cancer who received the CPA combination therapy. A total of 143 genetic polymorphisms in 13 candidate genes (CYP2B6, CYP2C9, CYP2C19, CYP3A4, CYP3A5, ALDH1A1, ALDH3A1, GSTA1, GSTM1, GSTP1, GSTT1, ABCC2 and ABCC4), possibly involved in the activation, metabolism and transport of CPA, were genotyped using 184 cases who developed either > or =grade 3 leukopenia/neutropenia or > or =grade 2 gastrointestinal toxicity and 219 controls who did not show any ADRs throughout the treatment. The association study revealed that one SNP, rs9561778 in ABCC4, showed a significant association with CPA-induced ADRs (Cochran-Armitage trend's P-value=0.00031; odds ratio (OR)=2.06). Subgroup analysis also indicated that the SNP rs9561778 was significantly associated with two major ADR subgroups; gastrointestinal toxicity and leukopenia/neutropenia (Cochran-Armitage trend's P-value=0.00019 and 0.014; OR=2.31 and 1.83). Furthermore, the SNP rs9561778 showed an association with breast cancer patients who were treated with CA(F) drug regimen-induced ADR (Cochran-Armitage trend's P-value=0.00028; OR=3.13). The SNPs in ABCC4 might be applicable in predicting the risk of ADRs in patients receiving CPA combination chemotherapy.
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56 In this study, we examined a total of 141 SNPs and two gene deletions in 13 candidate genes that were considered to be involved in the activation (CYP2B6, CYP2C9, Table 2 Continued MAF Cochran-Armitage HWE CHR Gene SNP Allele1 Allele2 Position/effect ADR Non-ADR trend P-value ADR Non-ADR 13 rs9590216 T C Intron 1 0.45 0.46 0.93 0.24 0.11 13 rs9561820 T C Intron 1 0.31 0.29 0.63 0.17 0.010 13 rs4148431 A G Intron 1 0.44 0.45 0.84 0.48 0.023 13 rs7328332 T C Intron 1 0.14 0.10 0.23 1.00 1.00 13 rs870004 A G Intron 1 0.18 0.26 0.063 0.69 0.65 13 rs8001475 C T Intron 1 0.29 0.35 0.24 0.78 0.45 13 rs4148426 G C Intron 1 0.18 0.25 0.11 0.68 0.34 13 rs9524873 A G Intron 1 0.26 0.22 0.40 0.25 0.010 13 rs4771910 C T Intron 1 0.30 0.35 0.40 0.58 0.70 13 rs10508017 T C Intron 1 0.24 0.23 0.83 0.34 0.025 13 rs4148424 T C Intron 1 0.34 0.36 0.56 0.61 1.00 13 rs4148422 C T Intron 1 0.37 0.36 0.92 0.80 0.26 13 rs34665760 A G Intron 1 0.24 0.30 0.21 0.75 0.84 13 rs4773872 T C Intron 1 0.28 0.36 0.084 0.40 0.57 13 rs4771912 G A Intron 1 0.24 0.33 0.045 1.00 0.33 13 rs4773875 T G Intron 1 0.43 0.35 0.10 0.34 0.70 13 rs8001444 T C Intron 1 0.37 0.47 0.041 0.80 1.00 17 ALDH3A1 rs758427 T C 5' near gene 0.49 0.49 0.88 0.82 0.73 17 rs11657205 T C 5' near gene 0.49 0.48 0.82 1.00 0.49 17 rs11204411 C T 5' near gene 0.20 0.22 0.67 1.00 0.45 17 rs57555435 A G Exon 10 syn. 0.14 0.14 0.85 0.34 0.040 17 rs2228100 G C Ala329Pro 0.32 0.33 0.82 1.00 0.85 17 rs3744692 A G Glu309Gly 0.03 0.05 0.36 1.00 1.00 17 rs2072330 A T Exon 6 syn. 0.45 0.44 0.83 0.64 0.06 17 rs887241 T G Ala134Ser 0.03 0.04 0.73 1.00 1.00 19 CYP2B6 rs7254579 C T 5' near gene 0.46 0.49 0.57 0.24 0.24 19 rs4802101 T C 5' near gene 0.39 0.32 0.17 0.81 0.56 19 rs4803415 T C Intron 1 0.23 0.19 0.35 0.52 0.28 19 rs4803419 T C Intron 3 0.45 0.49 0.49 0.64 0.61 19 rs3745274 T G His172Gln 0.13 0.17 0.32 1.00 1.00 19 rs2279343 G A Arg262Lys 0.16 0.22 0.13 1.00 0.81 19 rs2279345 T C Intron 5 0.36 0.31 0.28 1.00 0.32 19 rs7255374 T C Intron 8 0.19 0.22 0.51 1.00 0.80 19 rs1042389 C T 3' UTR 0.30 0.26 0.46 0.09 0.83 GSTM1 and GSTT1 deletion ADR Non-ADR Gene Deletion Wildtype Deletion Wildtype Fisher`s exact P-value Odds ratio GSTM deletion 46 51 102 87 0.32 0.769 GSTT deletion 41 56 83 108 0.90 0.953 Abbreviations: ADR, adverse drug reaction; HWE, Hardy-Weinberg equilibrium; MAF, minor allele frequency.
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ABCC4 p.His172Gln 19696793:56:1841
status: NEW