ABCB1 p.Thr522Ser
| Predicted by SNAP2: | A: D (85%), C: D (85%), D: D (91%), E: D (91%), F: D (91%), G: D (91%), H: D (91%), I: D (91%), K: D (91%), L: D (91%), M: D (85%), N: D (91%), P: D (95%), Q: D (91%), R: D (95%), S: D (71%), V: D (91%), W: D (91%), Y: D (91%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: D, G: D, H: D, I: D, K: D, L: D, M: D, N: D, P: D, Q: D, R: D, S: D, V: D, W: D, Y: D, |
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[hide] The influence of genetic polymorphisms in MDR1 gen... Med Oncol. 2013;30(3):601. doi: 10.1007/s12032-013-0601-0. Epub 2013 May 21. Jia Y, Tian W, Sun S, Han P, Xue W, Li M, Liu Y, Jiang S, Cui B
The influence of genetic polymorphisms in MDR1 gene on breast cancer risk factors in Chinese.
Med Oncol. 2013;30(3):601. doi: 10.1007/s12032-013-0601-0. Epub 2013 May 21., [PMID:23690268]
Abstract [show]
Breast cancer (BC) is the most common cancer among women in the world. The human multidrug resistance 1 gene (MDR1) is potentially an important gene influencing the susceptibility to breast cancer. This study aimed to assess the association of MDR1 genetic polymorphisms with the susceptibility to BC. Overall, 353 BC patients and 360 cancer-free controls were enrolled. The clinical characteristics were summarized by questionnaires. The c.1564A > T genetic polymorphism was genotyped using created restriction site-polymerase chain reaction method. We found that no significant differences in the genotypic and allelic frequencies between BC patients and cancer-free controls. Furthermore, the distribution of BC patients' risk factors was not significantly different among AA, AT, and TT genotypes. Our findings indicate that the c.1564A > T genetic polymorphism is not significantly associated with the susceptibility to BC in Chinese Han populations.
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45 T mutation and resulted in threonine (Thr) to serine (Ser) amino acid replacement (p.Thr522Ser).
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ABCB1 p.Thr522Ser 23690268:45:85
status: NEW[hide] Association between single genetic polymorphisms o... Med Oncol. 2013;30(3):643. doi: 10.1007/s12032-013-0643-3. Epub 2013 Jun 26. Qiao W, Wang T, Zhang L, Tang Q, Wang D, Sun H
Association between single genetic polymorphisms of MDR1 gene and gastric cancer susceptibility in Chinese.
Med Oncol. 2013;30(3):643. doi: 10.1007/s12032-013-0643-3. Epub 2013 Jun 26., [PMID:23801278]
Abstract [show]
Gastric cancer is a common cancer worldwide. The multidrug resistance 1 gene (MDR1) is one of the most important candidate genes for influencing gastric cancer susceptibility. This study aimed to analyze the association between genetic variants of MDR1 gene and the susceptibility to gastric cancer in Chinese Han population. A total of 365 gastric cancer patients and 367 cancer-free controls were enrolled in this study. The single genetic polymorphisms (SNPs) of MDR1 gene were genotyped by the created restriction site-polymerase chain reaction method. Our data suggested that the allele and genotype frequencies of c.159G > T and c.1564A > T were statistically different between gastric cancer patients and cancer-free controls. Association analyses indicated that these two SNPs were statistically associated with the increased risk of gastric cancer (for c.159G > T, TT versus (vs.) GG: OR 2.34, 95 % CI 1.31-4.19; TT vs. GT/GG: OR 2.32, 95 % CI 1.32-4.08; T vs. G: OR 1.27, 95 % CI 1.01-1.59; for c.1564A > T, TT vs. AA: OR 2.27, 95 % CI 1.31-3.93; TT vs. AT/AA: OR 2.21, 95 % CI 1.30-3.75; T vs. A: OR 1.30, 95 % CI 1.04-1.62). The allele-T of both these two SNPs may contribute to the susceptibility to gastric cancer in Chinese Han population. The c.159G > T and c.1564A > T genetic variants might be used as molecular markers for detecting gastric cancer susceptibility.
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43 As for the c.1564A [ T SNP, it is a nonsynonymous mutation and causes by A to T mutations, which resulted in threonine (Thr) to serine (Ser) amino acid replacement (p.Thr522Ser, reference sequences: GenBank IDs: NG_011513.1, NM_000927.4, and NP_000918.2).
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ABCB1 p.Thr522Ser 23801278:43:167
status: NEW[hide] Association between the c.1564A>T genetic polymorp... Genet Mol Res. 2014 Aug 29;13(3):6820-6. doi: 10.4238/2014.August.29.3. Wan YY, Wang XW, Hui HX, Wan L
Association between the c.1564A>T genetic polymorphism of the MDR1 gene and hepatocellular carcinoma in Chinese population.
Genet Mol Res. 2014 Aug 29;13(3):6820-6. doi: 10.4238/2014.August.29.3., [PMID:25177961]
Abstract [show]
The objective of this study was to evaluate the influence of c.1564A>T genetic polymorphisms in the multidrug resistance 1 gene (MDR1) on hepatocellular carcinoma (HCC) susceptibility through association analysis. A total of 632 HCC patients and 645 cancer-free controls were enrolled in this study. The c.1564A>T genetic polymorphisms were genotyped by created restriction site-polymerase chain reaction (CRS-PCR) and confirmed using DNA sequencing methods. The potential associations of c.1564A>T genetic polymorphisms with the risk of HCC were analyzed by different genetic models. Statistically significantly increased risks of HCC were detected in the homozygote comparison (TT versus AA: OR = 1.70, 95%CI = 1.17-2.45, chi(2) = 7.99, P = 0.005), recessive model (TT versus AT/AA: OR = 1.64, 95%CI = 1.15-2.33, chi(2) = 7.66, P = 0.006), and allele contrast (T versus A: OR = 1.23, 95%CI = 1.04-1.45, chi(2) = 6.09, P = 0.014). Our data suggest that the genotypes/alleles from c.1564A>T genetic polymorphisms are statistically associated with HCC risk. The allele-T and genotype TT may contribute to susceptibility to HCC in the Chinese Han population.
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45 The sequence analyses indicated that this genetic polymorphism was a non-synonymous mutation, which was caused by A to T mutations in exon15 of MDR1, leading to the threonine (Thr) to Serine (Ser) amino acid replacement (p.Thr522Ser).
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ABCB1 p.Thr522Ser 25177961:45:223
status: NEW72 Our sequence analyses indicated that the c.1564A>T genetic polymorphism caused a p.Thr522Ser amino acid replacement.
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ABCB1 p.Thr522Ser 25177961:72:83
status: NEW[hide] XRCC1 genetic polymorphism acts a potential biomar... Tumour Biol. 2015 May;36(5):3745-50. doi: 10.1007/s13277-014-3014-6. Epub 2015 Jan 8. Zhu DQ, Zou Q, Hu CH, Su JL, Zhou GH, Liu P
XRCC1 genetic polymorphism acts a potential biomarker for lung cancer.
Tumour Biol. 2015 May;36(5):3745-50. doi: 10.1007/s13277-014-3014-6. Epub 2015 Jan 8., [PMID:25563194]
Abstract [show]
Lung cancer is one of the most common but serious cancers in the world. Both the X-ray repair cross-complementing group 1 (XRCC1) gene and the human multidrug resistance 1 (MDR1) gene are important candidate genes influencing the susceptibility to various diseases, including lung cancer. This study aimed to assess the correlation of genetic polymorphisms in XRCC1 and MDR1 with the susceptibility to lung cancer. In this study, a total of 320 lung cancer patients and 346 cancer-free controls in Chinese population were enrolled in this study. Data about the clinical characteristics and related risk factors of lung cancer were collected by questionnaires. The single-nucleotide polymorphisms (SNPs) of XRCC1 and MDR1 genes were genotyped by created restriction site-polymerase chain reaction method. Our data showed that the risk for lung cancer increased significantly among the variant Arg194Trp (C > T, rs1799782) and Arg399Gln (G > A, rs25487) of XRCC1, but there are no significant differences in the allelic and genotypic frequencies of c.1564A > T and c.3073A > C of MDR1 between lung cancer patients and cancer-free controls. In conclusion, these preliminary results suggest that the C > T, rs1799782 and C > T, rs25487 of XRCC1 genetic variants might be used as molecular markers for detecting lung cancer susceptibility.
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44 We found that all of these genetic variants were non-synonymous mutations, C > T, rs1799782 in exon6 of XRCC1 resulting in a arginine (Arg) to tryptophan (Trp) acid replacement (p. Arg 194 Trp), G > A, rs25487 in exon10 of XRCC1 resulting in a arginine (Arg) to glutamine (Gln) acid replacement (p. Arg 399 Gln), c.1564A > T in exon15 of MDR1 resulting in threonine (Thr) to serine (Ser) amino acid replacement (p. Thr 522 Ser) and c.3073A > C in exon22 of MDR1 resulting in a leucine (Leu) to phenylalanine (Phe) acid replacement (p.Leu 860 Phe).
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ABCB1 p.Thr522Ser 25563194:44:415
status: NEW[hide] Genetic polymorphisms of the multidrug resistance ... Tumour Biol. 2015 Aug;36(9):7007-15. doi: 10.1007/s13277-015-3407-1. Epub 2015 Apr 12. Wang ZC, Liu LZ, Liu XY, Hu JJ, Wu YN, Shi JY, Yang LX, Duan M, Wang XY, Zhou J, Fan J, Gao Q
Genetic polymorphisms of the multidrug resistance 1 gene MDR1 and the risk of hepatocellular carcinoma.
Tumour Biol. 2015 Aug;36(9):7007-15. doi: 10.1007/s13277-015-3407-1. Epub 2015 Apr 12., [PMID:25861753]
Abstract [show]
A possible association between multiple drug resistance 1 gene (MDR1) polymorphisms and the risk of developing hepatocellular carcinoma (HCC) is currently under debate, and evidence from various epidemiological studies has yielded controversial results. To derive a more precise estimation of the association between MDR1 polymorphisms and HCC risk, the present meta-analysis was performed. A total of 8 studies containing 11 cohorts with 4407 cases and 4436 controls were included by systematic literature search of EMBASE, PubMed, Web of Science, and CNKI. All polymorphisms were classified as mutant/wild-type alleles. In particular, the variation type, functional impact, and protein domain location of the polymorphisms were assessed and used as stratified indicators. The pooled odds ratio (OR) with 95 % confidence interval (CI) was calculated to evaluate the association. Overall, our results suggested that the mutant alleles of the MDR1 gene were associated with a significantly increased risk for HCC under all genetic models (allelic model: OR = 1.28, 95 % CI = 1.20-1.36, P < 0.001; dominant model: OR = 1.27, 95 % CI = 1.16-1.38, P < 0.001; recessive model: OR = 1.59, 95 % CI = 1.36-1.85, P < 0.001). Furthermore, increased risks for HCC were also revealed in stratified analyses by ethnicity, sample size, and quality scores of cohorts as well as variation type, functional impact, and protein domain location of polymorphisms. In conclusion, the present meta-analysis suggested that the presence of MDR1 mutant alleles might be a risk factor for HCC.
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80 Positions in different coding Table 1 Characteristics of the studies and cohorts included in the meta-analysis Name of studies Country Ethnicity Type of case/control Genotyping method Quality scores Age Male/female ratio Variant site Genotype frequency of case/control HWE Case Control Case Control 1/1 1/2 2/2 Mean SD Mean SD Chen Y [29] China Chinese HCC a /HP PCR-RFLP 6 55.8 14.7 54.5 13.9 91/9 90/10 2677G>T/A 18/19 56/53 26/28 0.492 Minoru F-1 [30] Japan Japanese HCC b /HP PCR-SSCP 8 70 7 - - 43/15 61 2677G>T/A 12/16 29/30 17/15 0.900 Minoru F-2 [30] Japan Japanese HCC b /HP PCR-SSCP 8 70 7 - - 43/15 61 3435C>T 16/14 29/39 13/8 0.023 Ren YQ [31] China Chinese HCC a /HP CRS-PCR 7 58.7 11.3 55.8 15.6 512/177 499/181 4125A>C 299/312 289/303 101/65 0.487 Gao J-1 [32] China Chinese HCC a /HP CRS-PCR 7 57.9 13.7 53.5 14.9 278/75 269/66 335T>C 141/172 150/128 62/35 0.132 Gao J-2 [32] China Chinese HCC a /HP CRS-PCR 7 57.9 13.7 53.5 14.9 278/75 269/66 3073A>C 116/155 158/139 79/41 0.261 Rui J [33] China Chinese HCC a /HP MALDI-TOF-MS 8 46 - 48 - 95/14 90/19 1236C>T 19/22 54/48 36/39 0.310 Yang D-1 [34] China Chinese HCC a /HP CRS-PCR 8 59.2 14.3 58.3 15.3 418/287 429/297 159G>T 312/342 298/308 95/76 0.591 Yang D-2 [34] China Chinese HCC a /HP CRS-PCR 8 59.2 14.3 58.3 15.3 418/287 429/297 1465C>T 294/367 306/292 105/67 0.420 Li XF [35] China Chinese HCC a /HP CRS-PCR 8 58.6 14.5 59.1 13.5 409/236 445/213 3751G>A 283/325 271/286 91/47 0.136 Wan YY [36] China Chinese HCC a /HP CRS-PCR 8 57.7 13.2 58.6 14.2 399/233 435/210 1564A>T 278/311 266/276 88/58 0.772 Total 4407 4436 1788/2055 1906/1902 713/479 1/1, 1/2, and 2/2 represent wild homozygous genotype, wild/mutant heterozygous genotype, and mutant homozygous genotype, respectively HCC hepatocellular carcinoma, HP healthy people, CHC chronic hepatitis C, CHB chronic hepatitis B, B-^ unclear, PCR-RFLP polymerase chain reaction-restriction fragment length polymorphism, PCR-SSCP polymerase chain reaction-single-strand conformation polymorphism, CRS-PCR created restriction site-polymerase chain reaction, MALDI-TOF-MS matrix-assisted laser desorption ionization timeof-flight mass spectrometry a Hepatitis B-related HCC b Hepatitis C-related HCC Table 2 Characteristics of the MDR1 polymorphisms included in the meta-analysis Studies Polymorphism site Exon location Variation type A.A. alteration FI a FI score a Feature key P. location description b P. function description b Chen Y [29] 2677G>T/A Exon 21 Nonsynonymous S893A Neutral -0.98 Topological domain Cytoplasmic ABC transmembrane type 1 S893T Low 1.66 Topological domain Cytoplasmic ABC transmembrane type 1 Minoru F-1 [30] 2677G>T/A Exon 21 Nonsynonymous S893A Neutral -0.98 Topological domain Cytoplasmic ABC transmembrane type 1 S893T Low 1.66 Topological domain Cytoplasmic ABC transmembrane type 1 Minoru F-2 [30] 3435C>T Exon 26 Synonymous - - - Topological domain Cytoplasmic ABC transporter Ren YQ [31] 4125A>C Exon 28 Nonsynonymous E1211A Low 1.805 Topological domain Cytoplasmic ABC transporter Gao J-1 [32] 335T>C 5'-UTR Noncoding - - - - - - Gao J-2 [32] 3073A>C Exon 22 Nonsynonymous L860F Medium 2.715 Transmembrane Helical ABC transmembrane type 1 Rui J [33] 1236C>T Exon 12 Synonymous - - - Topological domain Cytoplasmic ABC transporter Yang D-1 [34] 159G>T Exon 5 Synonymous - - - Transmembrane Helical ABC transmembrane type 1 Yang D-2 [34] 1465C>T Exon 14 Nonsynonymous R489C Medium 1.97 Topological domain Cytoplasmic ABC transporter Li XF [35] 3751G>A Exon 28 Nonsynonymous V1251I Neutral -0.365 Topological domain Cytoplasmic ABC transporter Wan YY [36] 1564A>T Exon 15 Nonsynonymous T522S Low 1.42 Topological domain Cytoplasmic ABC transporter A.A. amino acid, FI functional impact, ABC ATP-binding cassette a The functional impact is evaluated using online MutationAssessor.org b Location of SNP in the protein structure is assessed by Uniprot.org online service sequence subgroup analyses revealed that cytoplasmic polymorphisms correlated with a significantly higher HCC risk (cytoplasmic subgroup: OR=1.28, 95 % CI 1.19-1.37; P<0.00001), whereas transmembrane polymorphisms exhibited site-specific results (Gao J-2, 2013: OR=1.65, 95 % CI 1.32-2.05, P<0.0001; Yang D-1, 2013: OR=1.65, 95 % CI 0.98-1.33, P=0.10).
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ABCB1 p.Thr522Ser 25861753:80:3643
status: NEW