ABCB1 p.Leu860Phe
| Predicted by SNAP2: | A: N (72%), C: N (87%), D: D (66%), E: D (66%), F: N (57%), G: D (63%), H: D (59%), I: N (87%), K: D (66%), M: N (82%), N: D (63%), P: D (66%), Q: D (59%), R: D (66%), S: D (53%), T: N (61%), V: N (97%), W: D (59%), Y: D (59%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: D, G: D, H: D, I: N, K: D, M: N, N: D, P: D, Q: D, R: D, S: D, T: D, V: N, W: D, Y: D, |
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[hide] Investigation on MDR1 gene polymorphisms and its r... Med Oncol. 2013 Mar;30(1):375. doi: 10.1007/s12032-012-0375-9. Epub 2013 Jan 10. Fang Y, Zhao Q, Ma G, Han Y, Lou N
Investigation on MDR1 gene polymorphisms and its relationship with breast cancer risk factors in Chinese women.
Med Oncol. 2013 Mar;30(1):375. doi: 10.1007/s12032-012-0375-9. Epub 2013 Jan 10., [PMID:23307242]
Abstract [show]
The human multidrug resistance 1 gene (MDR1) is an important candidate gene influencing the susceptibility to various diseases, including breast cancer. The object of this study was to investigate on MDR1 gene polymorphisms and its relationship with the susceptibility to breast cancer. A total of 271 patients with breast cancer and 225 healthy controls were enrolled in this study. Data about the risk factors for breast cancer were collected using questionnaires. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing methods were used to investigate the c.3073A > C polymorphisms. We observed no significant differences in the allelic and genotypic frequencies of c.3073A > C polymorphisms between patients and control subjects. Furthermore, there were no significant differences about the distribution of the breast cancer patients' risk factors among AA, AC and CC genotype. Results from this study suggested that c.3073A > C polymorphism was not associated with the susceptibility to breast cancer in the studied population. Future studies evaluating the association between c.3073A > C variant and breast cancer risks are essential to reach to more reliable results on larger populations.
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38 This variant is a nonsynonymous mutation, Table 1 Primer pairs, PCR and PCR-RFLP analysis for MDR1 gene SNP Primer sequences Annealing temperature (&#b0;C) Amplification fragment (bp) Region Restriction enzyme Genotype: bp c.3073A [ C 50 -TAGTCTCATGAAGGTGAGTTTTCAG-30 59.0 259 Exon22 MaeIII GG: 185, 74 50 -GTGCTTGTCCAGACAACATTTTC-30 GA: 259, 185, 74 AA: 259 Table 2 Genotypic and allelic frequencies of c.3073A [ C in the studied subjects Groups Genotypic frequencies (%) Allelic frequencies (%) AA AC CC A C Case group (n = 271) 130 (0.4797) 110 (0.4059) 31 (0.1144) 370 (0.6827) 172 (0.3173) Control group (n = 225) 102 (0.4533) 97 (0.4311) 26 (0.1156) 301 (0.6689) 149 (0.3311) v2 = 0.3714, p = 0.8305 v2 = 0.2129, p = 0.6445 resulting in a leucine (Leu) to phenylalanine (Phe) acid replacement (p.Leu860Phe, reference sequences GenBank ID: NG_011513.1, NM_000927.4 and NP_000918.2).
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ABCB1 p.Leu860Phe 23307242:38:803
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.Leu860Phe 25861753:80:3133
status: NEW