ABCB1 p.Arg489Cys
| Predicted by SNAP2: | A: N (53%), C: N (61%), D: D (80%), E: D (71%), F: D (66%), G: D (66%), H: D (53%), I: D (59%), K: N (72%), L: N (53%), M: N (53%), N: D (66%), P: D (80%), Q: D (53%), S: N (72%), T: N (53%), V: D (59%), W: D (75%), Y: D (71%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: D, G: D, H: D, I: D, K: N, L: D, M: D, N: D, P: D, Q: D, S: D, T: D, V: D, W: D, Y: D, |
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[hide] The association between genetic variant of MDR1 ge... Int Immunopharmacol. 2013 Sep;17(1):88-91. doi: 10.1016/j.intimp.2013.05.025. Epub 2013 Jun 10. Gao L, Yang Y, Song S, Hong H, Zhao X, Li D
The association between genetic variant of MDR1 gene and breast cancer risk factors in Chinese women.
Int Immunopharmacol. 2013 Sep;17(1):88-91. doi: 10.1016/j.intimp.2013.05.025. Epub 2013 Jun 10., [PMID:23759256]
Abstract [show]
Previous studies indicated that the human multidrug resistance 1 gene (MDR1) is an important candidate gene influencing the susceptibility to breast cancer. The purpose of this study was to detect the association between the MDR1 genetic variants and breast cancer susceptibility. A total of 647 subjects consisted of 322 patients with breast cancer and 325 cancer-free healthy controls were enrolled in this study. Data about the risk factors of breast cancer were summarized by questionnaires. The c.1465C>T genetic variant in MDR1 were genotyped by created restriction site-PCR (CRS-PCR) and verified by DNA sequencing methods. No significant differences in the allelic and genotypic frequencies of c.1465C>T polymorphism were detected between breast cancer patients and healthy controls. Our data suggest that there are no significant differences about the distribution of the risk factors of breast cancer patients among CC, CT and TT genotypes. These preliminary results from this study indicate that the c.1465C>T variant is not significantly associated with breast cancer susceptibility in the studied populations.
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51 According to the DNA, mRNA, protein reference sequences of MDR1 gene (GenBank IDs: NG_011513.1, NM_000927.4 and NP_000918.2), the sequence analysis indicated that the c.1465C>T polymorphism was a nonsynonymous mutation, which was caused by C to T mutations and resulted in arginine (Arg) to cysteine (Cys) amino acid replacement (p.Arg489Cys).
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ABCB1 p.Arg489Cys 23759256:51:332
status: NEW[hide] Relationship between multidrug resistance 1 polymo... Genet Mol Res. 2013 Sep 19;12(3):3806-12. doi: 10.4238/2013.September.19.12. Shen FR, Yan CY, Liu M, Feng YH, Chen YG
Relationship between multidrug resistance 1 polymorphisms and the risk of prostate cancer in Chinese populations.
Genet Mol Res. 2013 Sep 19;12(3):3806-12. doi: 10.4238/2013.September.19.12., [PMID:24085442]
Abstract [show]
Prostate cancer is one of the most common malignancies in men. The multidrug resistance 1 gene (MDR1) is an important candidate gene for prostate cancer. The aim of this study was to evaluate the association between MDR1 gene polymorphisms and the risk of prostate cancer. MDR1 gene polymorphism and its association with the risk of prostate cancer were investigated in 357 Chinese men. A novel c.1465C>T polymorphism was detected with created restriction site-polymerase chain reaction and DNA sequencing. We found a significantly increased risk of prostate cancer in the homozygote comparison [TT vs CC: odds ratio (OR) = 2.300, 95% confidence interval (95%CI) = 1.261-4.196, chi-square = 7.53, P = 0.007], heterozygote comparison (TC vs CC: OR = 1.667, 95%CI = 1.049-2.648, chi-square = 4.71, P = 0.030), dominant model (TT/TC vs CC: OR = 1.835, 95%CI = 1.197-2.815, chi-square = 7.81, P = 0.005), recessive model (TT vs TC/CC: OR = 1.776, 95%CI = 1.023- 3.085, chi-square = 4.23, P = 0.041), and allele contrast (T vs C: OR = 1.625, 95%CI = 1.199-2.202, chi-square = 9.87, P = 0.002). These findings suggested that the c.1465C>T polymorphism of MDR1 may be risk factors for prostate cancer in Chinese men.
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38 Sequence analysis showed that the c.1465C>T polymorphism was caused by a C to T mutation, resulting in arginine (Arg) to cysteine (Cys) amino acid replacement (p.Arg489Cys; reference sequences GenBank IDs NG_011513.1, NM_000927.4, and NP_000918.2).
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ABCB1 p.Arg489Cys 24085442:38:162
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.Arg489Cys 25861753:80:3426
status: NEW