ABCMdb

ABCB1 p.Ser893Ala

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Publications

PMID: 18855611 [PubMed] Zhou SF et al: "Clinical pharmacogenetics and potential application in personalized medicine."

No. Sentence Comment

532 Nucleotide change rs number Amino acid change 49T>C rs28381804 F17L 61A>G rs61615398; rs9282564 N21D 131A>G rs1202183 N44S 178A>C rs41315618 I60L 239C>A rs9282565 A80E 266T>C Rs35810889 M89T 431T>C rs61607171 I144T 502G>A rs61122623 V168I 548A>G rs60419673 N183S 554G>T rs1128501 G185V 781A>G rs36008564 I261V 1199G>A rs2229109 S400N 1696G>A rs28381902 E566K 1777C>T rs28381914 R593C 1778G>A rs56107566 R593H 1795G>A rs2235036 A599T 1837G>T rs57001392 D613Y 1985T>G rs61762047 L662R 2005C>T rs35023033 R669C 2207A>T rs41316450 I736K 2398G>A rs41305517 D800N 2401G>A rs2235039 V801M 2485A>G rs2032581 I829V 2506A>G rs28381967 I836V 2547A>G rs36105130 I849M 2677T>A/G rs2032582 S893A/T 2975G>A rs56849127 S992N 3151C>G rs28401798 P1051A 3188G>C rs2707944 G1063A 3262G>A rs57521326 D1088N 3295A>G rs41309225 K1099E 3320A>C rs55852620 Q1107P 3322T>C rs35730308 W1108R 3410G>T rs41309228 S1137I 3421T>A rs2229107 S1141T 3502A>G rs59241388 K1168E 3669A>T rs41309231 E1223D 3751G>A rs28364274 V1251I 3767C>A r35721439 T1256K Data are from NCBI dbSNP (access date: 2 August 2008). Login to comment

PMID: 11266082 [PubMed] Ito S et al: "Polymorphism of the ABC transporter genes, MDR1, MRP1 and MRP2/cMOAT, in healthy Japanese subjects."

No. Sentence Comment

56 In addition to T1236C, T to G transversion at position 2677, which is a missense mutation (Ser to Ala at codon 893), was reported as a natural mutation. Login to comment

PMID: 12426521 [PubMed] Siegmund W et al: "The effects of the human MDR1 genotype on the expression of duodenal P-glycoprotein and disposition of the probe drug talinolol."

No. Sentence Comment

97 In fact, substitution of alanine for serine at position 893 of AdrR MCF-7 cells resulted in a different multidrug-resistance pattern.37 In our study both variants in cDNA position 2677 changed neither duodenal MDR1 mRNA expression nor duodenal content of P-glycoprotein. Login to comment

PMID: 16103896 [PubMed] Thompson JF et al: "An association study of 43 SNPs in 16 candidate genes with atorvastatin response."

No. Sentence Comment

5 The only significant associations with LDL-C lowering were found with apoE2 in which carriers of the rare allele who took atorvastatin lowered their LDL-C by 3.5% more than those homozygous for the common allele and with rs2032582 (S893A in ABCB1) in which the two groups of homozygotes differed by 3% in LDL-C lowering. Login to comment
57 N ¼ 160 Cauc. N ¼ 2454 Hisp. N ¼ 85 Best P Statin Ref. ABC B1 rs2229109 7 86 824 460 Ser400Asn 0 1.2 3.8 1.8 rs2032582 7 86 805 269 Ser893Ala 40.0 89.4 56.7 60.2 rs17149694 7 86 783 310 Ser1141Thr 0 6.2 0.02 0.6 rs1045642 7 86 783 296 Ile1145Ile 50.0 79.0 48.7 50.0 0.023 Atorva 9 ABC G5 rs6720173 2 43 952 052 Gln604Glu 20.8 33.1 16.8 32.5 ABC G8 rs11887534 2 43 977 898 Asp19His 1.4 3.9 5.4 6.6 0.036 Atorva 17 rs4148211 2 43 983 394 Tyr54Cys 29.2 23.1 37.4 32.5 rs4148217 2 44 011 334 Thr400Lys 10.0 24.0 18.1 30.1 rs6544718 2 44 016 576 Val632Ala 6.9 5.9 21.8 18.7 ACE rs4331 17 58 917 784 Ala157Ala 72.2 43.2 43.8 53.0 0.005 Fluva 18 rs4341 17 58 919 722 72.2 43.8 44.0 51.9 0.005 Fluva 18 Apo AI rs670 11 116 213 623 Promoter G/A 20.8 14.4 16.4 21.1 HDLC Prava 19 ApoE rs429358 19 50 103 781 E4 (Cys130Arg) 8.3 29.0 17.7 17.7 0.043 Lova 20 rs7412 19 50 103 919 E2 (Cys176Arg) 2.8 5.0 3.7 1.2 0.01 Atorva 21 19 50 106 239 SNP17 5.6 13.5 7.3 2.4 5 CETP rs1800775 16 55 552 735 CÀ629A 51.6 57.3 48.2 48.1 HDLC Atorva 22 rs708272 16 55 553 789 TaqIB 46.8 25.7 42 42.5 HDLC Atorva 22 Cyp3A4 rs4986910 7 99 003 175 Met445Thr 0 0.9 0.8 0 0.05 Atorva 23 rs2740574 7 99 026 747 AÀ392G 4.7 56.2 3.9 11.4 0.038 Atorva 23 Cyp3A5 rs776746 7 98 915 190 *3 40.6 64.2 7.4 27.2 0.026 24 rs10264272 7 98 907 486 *6, Lys208Lys 1.6 8.7 0.07 3.2 Cyp7A1 rs3808607 8 59 575 478 33.3 56.8 39.3 31.9 0.001 Atorva 25 FDFT1 rs2686196 8 11 697 311 0 0.6 1.4 0.6 HMGCR 5 74 681 677 Asn204Ser 0.0 0.0 0.2 0.0 rs5908 5 74 687 955 Val638Ser 0.0 0.3 1.7 1.2 rs2303151 5 74 691 457 11.1 2.9 4.9 4.8 5 74 691 504 SNP29 0.0 8.5 2.8 2.9 0.003 Prava 5 LDLR rs5925 19 11 091 881 Val653Val, AvaII 40.3 23.1 47.0 56.7 0.05 Fluva 26 rs688 19 11 088 602 Asn591Asn, HincII 36.1 13.0 46.8 46.3 LIPC rs1800588 15 56 510 967 CÀ514T 40.3 49.1 23.1 45.7 0.01 Prava 27 LPL rs1801177 8 19 849 988 Asp9Asn 0 3.9 1.3 1.2 rs268 8 19 857 809 Asn291Ser 0 0.3 1.7 0.6 rs328 8 19 864 004 Ser447X 11.1 8.2 11.2 9.1 OATP C 12 21 185 236 CÀ540T 5.6 3.8 5.0 10.8 12 21 216 983 *2, Phe73Leu 0 0 0.04 0 rs2291073 12 21 217 081 25.0 52.4 8.3 10.0 rs4149036 12 21 219 007 31.9 49.4 21.0 20.5 rs2306283 12 21 221 005 Asn130Asp, *1b 61.1 74.4 40.6 40.9 PK Prava 28 rs11045819 12 21 221 080 Pro155Thr, *4 2.8 9.7 15.8 8.5 rs4149056 12 21 222 816 Val174Ala, *5 8.3 3.8 16.0 14.5 PK Prava 28 12 21 250 200 Gly488Ala, *9 0 5.0 0 0 rs4149080 12 21 268 826 29.2 15.4 17.4 15.2 12 21 283 243 Leu643Phe 1.4 5.3 5.8 3.7 The genes and SNPs examined are listed in columns 1 and 2 with dbSNP identifiers, if available. Login to comment

PMID: 18287207 [PubMed] Gow JM et al: "Substrate-dependent effects of human ABCB1 coding polymorphisms."

No. Sentence Comment

21 The majority of pharmacogenetic studies for P-gp have focused on two polymorphisms, the synonymous 3435CϾT variation and the nonsynonymous 2677GϾT (S893A) variation (Schwab et al., 2003; Marzolini et al., 2004; Pauli-Magnus and Kroetz, 2004; Salama et al., 2006; Schaefer et al., 2006). Login to comment

PMID: 18370847 [PubMed] Oertel B et al: "Genetic mutations that prevent pain: implications for future pain medication."

No. Sentence Comment

159 Protein Chromosome Gene Gene position Variant as given in respective publications (reference ID if available) Transcriptional effect Minorallele frequency (%) Ref. MC1R 16q24.3 MC1R Exon 1 451C>T (rs1805007) Arg151-to-Cys (R151C) 2 [78] Exon 1 478C>T (rs1805008) Arg160-to-Trp (R160W) 2 Exon 1 880G>C (rs1805009) Asp294-to-His (D294H) - - 29insA - 2 Exon 1 178G>T (rs1805005) Val60-to-Leu (V60L) - Exon 1 252C>A (rs1805006) Asp84-to-Glu (D84E) - Exon 1 274G>A (rs2228479) Val92-to-Met (V92M) - Exon 1 488G>A (rs885479) Arg163-to-Gln (R163Q) - COMT 22q11.21 COMT Exon 4 472G>A (rs4680) Val158-to-Met (V158M) - [110] CYP2D6 22q13.1 CYP2D6 Exon 5 *3 2549A>del 260X [111] 2 [92] Exon 4 *4 1846G>A 182X [111] 20.7 - *5 chromosomal gene deleted - 2 Exon 3 *6 1707T>del (rs5030655) Trp152-to-Ter (W152X) 0.9 Exon 6 *7 2935A>C (rs5030867) His324-to-Pro (H324P) 0.1 Exon 3 *8 1758G>T 169X [111] 0 - Gene duplication/amplification - 2 Exon 5 *9 2613-5delAGA (rs28371720) Lys281-to-del (K281del) 1.8 Exon 1 *10 100C>T,188C>T (rs1065852) Pro34-to-Ser (P34S) 1.5 Intron 6 *41 2988G>A (rs28371725) - 8.4 [112] ABCB1 7q21.1 ABCB1 Exon 12 1236C>T (rs1128503) Gly412-to-Gly (G412G) 44 [113] Exon 22 2677G>T/A (rs2032582) Ser893-toAla/Thr (S893A/T) 42(T), 0.5(A) Exon 27 3435C>T (rs1045642) Ile1145-to-Ile (I1145I) 50 Variants increasing the metabolism of prodrugs into active analgesics Cytochrome P450 2D6 gene Codeine has a 200-times lower affinity at µ-opioid receptors than morphine [89], and therefore its clinical effects largely depend upon its O-demethylation to morphine [9,10], which is mediated by CYP 2D6 [90], although some of its clinical effects appear to persist independently of morphine formation. Login to comment

PMID: 18424454 [PubMed] Levran O et al: "ABCB1 (MDR1) genetic variants are associated with methadone doses required for effective treatment of heroin dependence."

No. Sentence Comment

62 SNP rs2032582 (2677G/T/A) is non-synonymous (Ser893Ala/Thr), SNPs rs1045642 (3435C.T) and rs1128503 (1236C.T) are synonymous and the other six SNPs are intronic. Login to comment
89 ABCB1 single nucleotide polymorphisms (SNPs) analyzed in this study No. SNP Alleles Positiona Amino acid change Exon/intron (i) MAFb Map positionc HWE P-valued 1 rs1045642 C/T 3435 Ile1145Ile 26 0.45 86976581 0.8 2 rs6949448 A/G i25 0.43 86979750 0.7 3 rs2235067 G/A i22 0.07 86987858 0.8 4 rs2032583 C/T i21 0.08 86998497 0.8 5 rs2032582 G/T (A) 2677 Ser893Ala (Thr) 21 0.43 (0.02) 86998554 0.7 6 rs1922242 A/T i16 0.50 87011603 0.3 7 rs1128503 C/T 1236 Gly412Gly 12 0.42 87017537 0.6 8 rs2520464 A/G i4 0.45 87039022 0.6 9 rs3789243 C/T i3 0.49 87058822 0.4 HWE, Hardy-Weinberg equilibrium. Login to comment

PMID: 20177420 [PubMed] Glimelius B et al: "Prediction of irinotecan and 5-fluorouracil toxicity and response in patients with advanced colorectal cancer."

No. Sentence Comment

63 Genotyping of ABCB1 c.2677G4T/A (rs2032582), which leads to a change in amino acid 893 from serine to alanine or threonine, was performed according to Saito et al.44 Allelic discrimination of the synonymous ABCB1 polymorphisms c.1236C4T (rs1128503) and c.3435C4T (rs1045642) was performed using TaqMan SNP Genotyping Assay kits containing primers and probes (C__7586662_10 and C__7586657_1, Applied Biosystems). Login to comment

PMID: 20216335 [PubMed] Hodges LM et al: "Very important pharmacogene summary: ABCB1 (MDR1, P-glycoprotein)."

No. Sentence Comment

106 The three most common SNPs in the protein coding region are rs1128503 (1236T > C, Gly412Gly), rs2032582 (2677T > G/A, Ser893Ala/Thr), and rs1045642 (3435T > C, Ile1145Ile) [125], according to the National Center for Biotechnology Information build 130 of dbSNP. Login to comment
111 Rs2032582 (2677T > G/A, mRNA 3095T > G/A, Ser893Ala/Thr) The triallelic SNP, rs2032582 (2677T > G/A, Ser893Ala/ Thr), has been well studied because it is a common amino acid change in P-gp. Login to comment

PMID: 20938339 [PubMed] Sylvester RK et al: "Temozolomide-induced severe myelosuppression: analysis of clinically associated polymorphisms in two patients."

No. Sentence Comment

101 Although both patients were Table 1 Summary of genotyping results of the selected SNPsa SNP Case 1 Case 2 Genotype with increased riskb SNP typec Frequency in Caucasiand,e ABCB1 rs1045642 CT CT - Synonymous CC: 0.15, CT: 0.63, TT: 0.22 rs1128503 CT CT - Synonymous CC: 0.35, CT: 0.52, TT: 0.13 rs2032582 GT GT - missense (S893A) GG: 0.32, GT: 0.56, TT: 0.12 GSTP1 rs1695 AG AA AA missense (I105V) AA: 0.33, AG: 0.55, GG: 0.12 MGMT rs12917 CT CT - missense (L84F) CC: 0.78, CT: 0.20, TT: 0.02 rs1803965 GA GA - Synonymous GG: 0.85, GA: 0.14, AA: 0.02 rs2282164 CC CC - missense (W65C) CC 1.00, CG and GG are < 0.001 rs2308318 GG GG - missense (G160R) GG 1.00, AG is 0.007 globally, AA: 0.00 rs2308321 GG AA AG or GG missense (I143V) AA: 0.65, AG: 0.35; GG: 0.007 globally rs2308322 GG GG - missense (P58S) GG, 1.00, GA is 0.003 globally, AA 0.00 rs2308327 AG AA AG or GG missense (K178R) AA: 0.98, AG: 0.02, GG: 0.00 NQO1 rs1800566 GG GG GG missense (P187S) GG: 0.60, AG: 0.37, AA: 0.03 ABCB1, ATB-binding cassette subfamily B member 1; GSTP1, glutathione S-transferases pi 1; MGMT, O6 -methylguanine-DNA-methyltransferase; NQO1, NAD(P)H dehydrogenase (quinone) family; SNPs, single nucleotide polymorphisms; a Bold lettering denotes SNPs, which were found to be non-wild-type for the indicated patient. Login to comment

PMID: 21142916 [PubMed] Gasso P et al: "Xenobiotic metabolizing and transporter genes: gene-gene interactions in schizophrenia and related disorders."

No. Sentence Comment

26 Regarding ABCB1, although several exon polymorphisms have been identified, G2677T is a missense mutation (amino acid change Ser893Ala), whereas others such as C3435T are synonymous variants. Login to comment

PMID: 21625253 [PubMed] Wolf SJ et al: "An update on ABCB1 pharmacogenetics: insights from a 3D model into the location and evolutionary conservation of residues corresponding to SNPs associated with drug pharmacokinetics."

No. Sentence Comment

85 This non-synonymous SNP confers one of two amino-acid substitutions at position 893 (Ser893Ala/Thr). Login to comment
90 Many contradictory results are reported and as such no definitive conclusion has been Figure 3 Location and conservation of (a) E13/1236C4T (G412G), (b) E22/2677G4T/A (S893A/T) and (c) E27/3435C4T (I1145I). Login to comment
151 Of the remaining 10 previously associated SNPs, which can be mapped to the 3D structure, none reside in the substrate-binding region highlighted by Aller et al.12 Only one SNP, E8/554G4T (G185) (#ns7) resides within the membrane whereas another SNP (E22/2677G4T/A (S893A/ T) (#ns22)) resides in the region between the membrane and the cytosolic N-terminal NBD in the crystal structure, although this residue is part of TM10 (Figure 2). Login to comment

PMID: 20367534 [PubMed] Rodrigues AC et al: "Efflux and uptake transporters as determinants of statin response."

No. Sentence Comment

98 The ACCESS study showed an association between G2677T (S893A) single nucleotide polymorphism (SNP) and changes on LDL and total cholesterol after atorvastatin treatment [41]. Login to comment

PMID: 22705826 [PubMed] Rustemoglu A et al: "MDR1 gene polymorphisms may be associated with Behcet's disease and its colchicum treatment response."

No. Sentence Comment

104 Position Exon Amino acid change Allele BD (N=210) Control (N=260) P Genotype BD (105) Control (130) n F n F N p for HWE N p for HWE 1236 (rs1128503) 12 G412G C 109 0.524 121 0.465 0.3964 CC 33 0.0771 27 0.7270 CT 43 67 T 101 0.476 139 0.535 TT 29 36 2677 (rs2032582) 21 S893A/T G 104 0.495 124 0.477 0.5676 GG 26 0.9214 29 0.7323 GT 45 61 T 94 0.448 123 0.473 TT 22 27 A 12 0.057 13 0.050 TA 5 8 GA 7 5 3435 (rs1045642) 26 I1145I C 103 0.490 124 0.477 0.8739 CC 26 0.8449 33 0.2232 CT 51 58 T 107 0.510 136 0.523 TT 28 39 BD-Behcet's disease; n-number of alleles; N-number of subjects; F-frequency of alleles; HWE-Hardy-Weinberg equilibrium. Login to comment
103 Position Exon Amino acid change Allele BD (N=210) Control (N=260) P Genotype BD (105) Control (130) n F n F N p for HWE N p for HWE 1236 (rs1128503) 12 G412G C 109 0.524 121 0.465 0.3964 CC 33 0.0771 27 0.7270 CT 43 67 T 101 0.476 139 0.535 TT 29 36 2677 (rs2032582) 21 S893A/T G 104 0.495 124 0.477 0.5676 GG 26 0.9214 29 0.7323 GT 45 61 T 94 0.448 123 0.473 TT 22 27 A 12 0.057 13 0.050 TA 5 8 GA 7 5 3435 (rs1045642) 26 I1145I C 103 0.490 124 0.477 0.8739 CC 26 0.8449 33 0.2232 CT 51 58 T 107 0.510 136 0.523 TT 28 39 BD-Behcet's disease; n-number of alleles; N-number of subjects; F-frequency of alleles; HWE-Hardy-Weinberg equilibrium. Login to comment

PMID: 25881102 [PubMed] Lambrechts S et al: "Genetic variability in drug transport, metabolism or DNA repair affecting toxicity of chemotherapy in ovarian cancer."

No. Sentence Comment

111 The following 7 genetic variants failed genotyping: rs2032582 (Ser893Ala in ABCB1), rs2273697 (Val417Ile in ABCC2), rs1058930 (Ile194Met in CYP2C8), rs11572080 (Arg69Lyes in CYP2C8), rs10509681 (Lys329Arg in CYP2C8), rs12721627 (Thr185Ser in CYP3A4), rs25487 (Gln398Arg in XRCC1). Login to comment

PMID: 24505408 [PubMed] Noack A et al: "Drug-induced trafficking of p-glycoprotein in human brain capillary endothelial cells as demonstrated by exposure to mitomycin C."

No. Sentence Comment

126 In the MDR1 sequence of this construct we identified three of the most common single nucleotide polymorphisms, T1236C (Gly412Gly), T2677G (Ser893Ala) and T3435C (Ile1145Ile), which have been described in MDR1 of humans [24]. Login to comment

PMID: 24911077 [PubMed] Nahar R et al: "CYP2C9, VKORC1, CYP4F2, ABCB1 and F5 variants: influence on quality of long-term anticoagulation."

No. Sentence Comment

34 Nine variants in CYP2C9 (*2/rs1799853/430C>T/p.Cys144Arg in exon 3; *3/rs1057910/c.1075A>C/p.Ileu359Leu in exon 7; rs9332120, c.331+73T>C in intron 2; rs9332230, c.1291+53A>T in intron 8; rs2298037, c.1291+147C>T in intron 8; *14/rs72558189, c.374G>A/p.Arg125His in exon 2; rs9332172, c.820-73A>G in intron 5; rs1057911, c.1425A>T/p.Gly475Gly in exon 9; and c.610A>C, *57/p.Asn204His in exon 4), four variants in VKORC1 (1639G>A/g.3588G>A/rs9923231 in upstream promoter region; rs9934438, c.1173C>T in intron 2; rs7294, c.516G>A/ 3730G>A in 30 UTR and rs55894764/c.36G>A/p.Arg12Arg in exon 1), CYP4F2 rs2108622 (c.1297G>A/p.Val433Met in exon 11), three common polymorphisms in the MDR1/ABCB1 gene (rs1128503/ c.1236T>C/p.Gly412Gly in exon 12; rs2032582/c.2677T>G/A/ p.Ser893Ala/Thr in exon 21 and rs1045642/c.3435C>T/ p.Ile1145Ile in exon 26), APOE isoforms (e2, e3, e4 distinguished by two non synonymous polymorphisms; rs7212 and rs229358), factor V Leiden variant in F5 (rs6025/1691G>A/p.Arg506Gln) and prothrombin variant in F2 (rs1799963/20210G>A in 30 UTR) were genotyped. Login to comment

PMID: 24996502 [PubMed] Reiner Z et al: "Resistance and intolerance to statins."

No. Sentence Comment

66 The ACCESS trial also showed an association between G2677T (S893A) SNP and changes of total cholesterol as well as LDL-C plasma concentration after atorvastatin treatment [11]. Login to comment

PMID: 25591549 [PubMed] Tecza K et al: "Genetic polymorphisms and gene-dosage effect in ovarian cancer risk and response to paclitaxel/cisplatin chemotherapy."

No. Sentence Comment

61 Genotyping of polymorphic variants in PGR (rs10895068 and p.Val660Leu), ABCB1 (p.Ile1145 = and p.Ser893Ala/ Trp), ABCG2 (p.Gln141Lys), ATM (p.Asp1853Asn), TP53 (p.Arg72Pro), GSTP1 (p.Ile105Val) genes, as well as detection of GSTT1/M1 gene deletions, were performed as described previously [9-17]. Login to comment
101 The polymorphisms, which in univariate analysis were modulating ovarian cancer risk, were included in the Table 2 Case-control analyses of ovarian and breast and ovarian cancer risk Ovarian cancer all patients Ovarian cancer BRCA1- Ovarian cancer BRCA1+ Breast and ovarian cancer Gene polymorphism Genotype Controls n(%) n(%) OR (&#b1;95% CI) p n(%) OR (&#b1;95% CI) p n(%) OR (&#b1;95% CI) p n(%) OR (&#b1;95% CI) p PGR p.Val660Leu rs1042838 GG 239 (69.3) 143 (63.9) 1(ref) 131 (66.5) 1(ref) 12 (44.4) 1(ref) 46 (75.4) 1 (ref) GT 95 (27.5) 74 (33.0) 1.03 (0.90-1.88) 0.160 60 (30.5) 1.15 (0.78-1.70) 0.473 14 (51.9) 2.94 (1.31-6.58) 0.009 14 (23.0) 0.77 (0.40-1.46) 0.416 TT 11 (3.2) 7 (3.1) 1.06 (0.40-2.81) 0.901 6 (3.0) 1.00 (0.36-2.75) 0.993 1 (3.70) 1.81 (0.22-15.20) 0.584 1 (1.6) 0.47 (0.06-3.75) 0.478 GT + TT 106 (30.7) 81 (36.1) 1.20 (0.88-1.63) 0.249 66 (33.5) 1.14 (0.78-1.65) 0.504 15 (55.6) 2.82 (1.28-6.23) 0.010 15 (24.6) 0.74 (0.39-1.38) 0.336 ABCB1 p.Ser893Ala p.Ser893Thr rs2032582 GG 117 (33.7) 65 (29.0) 1(ref) 56 (28.4) 1(ref) 9 (33.4) 1(ref) 16 (26.2) 1 (ref) GT 156 (45.0) 115 (51.4) 1.33 (0.90-1.95) 0.152 104 (52.8) 1.39 (0.93-2.09) 0.108 11 (40.7) 0.92 (0.37-2.28) 0.852 33 (54.1) 1.55 (0.71-2.94) 0.184 TT 60 (17.3) 37 (16.5) 1.11 (0.67-1.85) 0.688 32 (16.3) 1.11 (0.65-1.90) 0.691 5 (18.5) 1.08 (0.35-3.38) 0.890 9 (14.8) 1.10 (0.46-2.63) 0.836 GA 9 (2.6) 2 (0.9) 0.40 (0.08-1.91) 0.250 2 (1.0) 0.46 (0.10-2.24) 0.337 - - - 2 (3.3) 1.63 (0.32-8.31) 0.557 TA 5 (1.4) 5 (2.2) 1.80 (0.50-6.45) 0.367 3 (1.5) 1.25 (0.29-5.49) 0.763 2 (7.4) 5.20 (0.87-31.18) 0.069 1 (1.6) 1.46 (0.16-13.6) 0.736 AA - - - - - - - - - - - - - GG + GT + GA 282 (81.3) 182 (81.3) 1 (ref) 162 (82.2) 1 (ref) 20 (74.1) 1 (ref) 51 (83.6) 1 (ref) TT + TA 65 (18.7) 42 (18.7) 1.00 (0.92-1.09) 1.000 35 (17.8) 0.94 (0.60-1.48) 0.780 7 (25.9) 1.52 (0.61-3.76) 0.364 10 (16.4) 0.85 (0.41-1.77) 0.664 ABCB1 p.Ile1145= rs1045642 CC 83 (24.0) 44 (19.6) 1(ref) 35 (17.8) 1(ref) 9 (33.3) 1(ref) 16 (26.2) 1 (ref) CT 162 (47.0) 122 (54.5) 1.42 (0.92-2.19) 0.113 112 (56.8) 1.64 (1.03-2.60) 0.036 10 (37.1) 0.57 (0.22-1.46) 0.239 26 (42.6) 0.83 (0.42-1.64) 0.596 TT 100 (29.0) 58 (25.9) 1.09 (0.67-1.78) 0.718 50 (25.4) 1.18 (0.70-2.00) 0.522 8 (29.6) 0.74 (0.27-2.00) 0.549 19 (31.2) 0.98 (0.48-2.04) 0.969 CT + TT 262 (76.0) 180 (80.4) 1.02 (0.81-1.30) 0.827 162 (82.2) 1.47 (0.94-2.28) 0.089 18 (66.7) 0.63 (0.27-1.46) 0.285 45 (73.8) 0.89 (0.48-1.66) 0.716 ABCG2 p. Gln141Lys rs2231142 CC 276 (80.2) 191 (86.4) 1 (ref) 167 (85.6) 1 (ref) 24 (92.3) 1 (ref) 56 (87.5) 1 (ref) CA 68 (19.8) 30 (13.6) 0.64 (0.40-1.02) 0.059 28 (14.4) 0.68 (0.42-1.10) 0.116 2 (7.7) 0.34 (0.08-0.47) 0.147 8 (12.5) 0.58 (0.26-1.28) 0.175 ATM p. Asp1853Asn rs1801516 GG 254 (75.8) 153 (68.6) 1 (ref) 134 (68.4) 1 (ref) 19 (70.4) 1 (ref) 45 (70.3) 1 (ref) GA 76 (22.7) 64 (28.7) 1.40 (0.95-2.06) 0.091 57 (29.1) 1.42 (0.95-2.13) 0.083 7 (25.9) 1.23 (0.50-3.05) 0.651 15 (23.4) 1.11 (0.59-2.11) 0.740 AA 5 (1.5) 6 (2.7) 1.99 (0.60-6.66) 0.262 5 (2.5) 1.90 (0.54-6.69) 0.319 1 (3.7) 2.67 (0.39-24.29) 0.380 4 (6.3) 4.52 (1.16-17.56) 0.029 GA + AA 81 (24.2) 70 (31.4) 1.43 (0.98-2.09) 0.061 62 (31.6) 1.45 (0.98-2.15) 0.062 8 (29.6) 1.32 (0.73-2.40) 0.352 19 (29.7) 1.32 (0.56-3.14) 0.528 TP53 p.Arg72Pro rs1042522 GG 167 (49.0) 130 (57.8) 1 (ref) 115 (58.1) 1 (ref) 15 (55.6) 1 (ref) 29 (48.3) 1 (ref) GC 150 (44.0) 79 (35.1) 0.68 (0.47-0.97) 0.031 70 (35.3) 0.68 (0.47-0.98) 0.039 9 (33.3) 0.67 (0.28-1.57) 0.355 29 (48.3) 1.11 (0.64-1.95) 0.707 CC 24 (7.0) 16 (7.1) 0.86 (0.44-1.68) 0.652 13 (6.6) 0.79 (0.39-1.61) 0.511 3 (11.1) 1.39 (0.38-5.16) 0.621 2 (3.3) 0.48 (0.11-2.14) 0.336 GC + CC 174 (51.0) 95 (42.2) 0.80 (0.61-1.05) 0.104 83 (41.9) 0.69 (0.49-0.99) 0.042 12 (44.4) 0.77 (0.35-1.69) 0.511 31 (51.67) 1.03 (0.59-1.78) 0.927 ATP7B p.Ser406Ala rs1801243 TT 103 (30.8) 41 (19.0) 1 (ref) 35 (18.5) 1 (ref) 6 (22.2) 1 (ref) 13 (20.3) 1 (ref) TG 157 (47.0) 113 (52.3) 1.81 (1.17-2.80) 0.008 100 (52.9) 1.87 (1.18-2.97) 0.007 13 (48.2) 1.42 (0.52-3.88) 0.490 32 (50.0) 1.61 (0.81-3.23) 0.174 GG 74 (22.2) 62 (28.7) 2.10 (1.28-3.46) 0.003 54 (28.6) 2.15 (1.27-3.62) 0.004 8 (29.6) 1.86 (0.61-5.61) 0.270 19 (29.7) 2.03 (0.94-4.40) 0.069 TG + GG 231 (69.2) 175 (81.0) 1.90 (1.26-2.88) 0.002 154 (81.5) 1.96 (1.27-3.03) 0.002 21 (77.8) 1.56 (0.61-3.99) 0.352 51 (79.7) 1.75 (0.91-3.36) 0.093 Table 2 Case-control analyses of ovarian and breast and ovarian cancer risk (Continued) ATP7B p.Arg952Lys rs732774 AA 103 (30.7) 86 (38.9) 1 (ref) 76 (39.2) 1 (ref) 10 (37.0) 1 (ref) 25 (39.7) 1 (ref) AG 159 (47.5) 96 (43.4) 0.72 (0.49-1.06) 0.096 82 (42.3) 0.70 (0.47-1.04) 0.078 14 (51.9) 0.91 (0.39-2.11) 0.821 31 (49.2) 0.80 (0.45-1.44) 0.471 GG 73 (21.8) 39 (17.7) 0.64 (0.39-1.04) 0.070 36 (18.5) 0.67 (0.41-1.10) 0.112 3 (11.1) 0.42 (0.11-1.61) 0.203 7 (11.1) 0.40 (0.16-0.97) 0.041 AG + GG 232 (69.3) 135 (61.1) 0.70 (0.49-1.00) 0.047 118 (60.8) 0.69 (0.48-1.00) 0.049 17 (63.0) 0.75 (0.33-1.71) 0.499 38 (60.3) 0.67 (0.39-1.18) 0.165 GST T1/M1 Gene deletions wt/wt 118 (34.6) 82 (36.8) 1(ref) 72 (36.7) 1(ref) 10 (37.0) 1(ref) 20 (31.3) 1(ref) wt/null 49 (14.4) 18 (8.1) 0.53 (0.29-0.98) 0.040 17 (8.7) 0.57 (0.30-1.07) 0.076 1 (3.7) 0.24 (0.03-1.96) 0.180 6 (9.4) 0.72 (0.27-1.92) 0.512 null/wt 138 (40.5) 95 (42.6) 0.99 (0.64-1.54) 0.967 82 (41.8) 0.97 (0.65-0.47) 0.90 13 (48.2) 1.11 (0.47-2.64) 0.810 31 (48.4) 1.32 (0.72-2.45) 0.368 null/null 36 (10.5) 28 (12.5) 1.12 (0.63-1.98) 0.698 25 (12.8) 1.14 (0.63-2.06) 0.667 3 (11.1) 0.98 (0.24-4.04) 0.982 7 (10.9) 1.14 (0.45-2.95) 0.774 GSTP1 p.Ile105Val rs1695 AA 151 (45.2) 104 (46.4) 1 (ref) 93 (47.2) 1 (ref) 11 (40.7) 1 (ref) 32 (52.4) 1 (ref) AG 162 (48.5) 95 (42.4) 0.85 (0.60-1.22) 0.376 84 (42.6) 0.84 (0.58-1.22) 0.361 11 (40.7) 0.93 (0.39-2.22) 0.873 36 (36.1) 0.64 (0.36-1.15) 0.137 GG 21 (6.3) 25 (11.2) 1.73 (0.92-3.26) 0.090 20 (10.2) 1.54 (0.79-3.01) 0.199 5 (18.6) 3.27 (1.03-10.42) 0.044 7 (11.5) 1.57 (0.61-4.03) 0.342 AG + GG 183 (54.8) 120 (53.6) 0.95 (0.68-1.34) 0.776 104 (52.8) 0.92 (0.65-1.32) 0.656 16 (49.3) 1.20 (0.54-2.67) 0.653 43 (47.6) 0.75 (0.43-1.29) 0.296 Statistically significant analyses are in bold. groups of risk reductors (favorable genotypes) or risk enhancers (unfavorable genotypes). 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111 Higher risk of disease progression was associated with presence of genotypes lacking a major p.Ser893Ala/Trp polymorphism (HR 2.14; 95% CI 1.07-4.28; p = 0.031) in the G allele of ABCB1 and with the presence of major homozygote GG of p.Asp1853Asn in the ATM gene (HR 2.32; 95% CI 1.06-5.10; p = 0.036) (Table 4). Login to comment
127 Similar results were also obtained for the rare heterozygotes TA of p. Ser893Ala/Trp polymorphism in ABCB1 gene. Login to comment
130 A. overall survival and risk of death for TP53 p.Arg72Pro; B. overall survival and risk of death for PGR p.Val660Leu; C. progression-free survival and cumulative risk of progression for unfavorable PFS factors (ATM p.Asp1853Asn GG genotype and ABCB1 p.Ser893Ala/Trp TT + TA genotypes group). Login to comment
131 Table 4 Progression-free survival/multivariate analysis/ Factor Variant Cases n (%) HR (&#b1;95% CI) P Histotype Non-serous 57 (44.2) 1 (ref) Serous 72 (55.8) 5.04 (2.05-12.37) 0.0004 FIGO 1 + 2 58 (46.0) 1 (ref) 3 + 4 68 (54.0) 2.19 (1.03-4.64) 0.041 ABCB1 p.Ser893Ala p.Ser893Thr rs2032582 Common allele carriers (GG + GT + GA) 101 (80.2) 1 (ref) Rare genotypes (AT + TT) 25 (19.8) 2.14 (1.07-4.28) 0.031 ATM p.Asp1853Asn rs1801516 Rare allele carriers (GA + AA) 87 (61.0) 1 (ref) Common homozygote (GG) 39 (39.0) 2.32 (1.06-5.10) 0.036 Statistically significant analyses are in bold. relevant compounds. Login to comment
167 As for the survival analyses, it was evident that accumulation of relatively weak genetic variants (ABCB1 p.Ser893Ala/ Trp and ATM p.Asp1853Asn) may significantly enhance the risk of progression after paclitaksel/cisplatin treatment. Login to comment
169 It should be noted that in recent large study performed on over four thousand invasive ovarian cancer patients the p.Ser893Ala/Trp polymorphism had no impact on patients` survival [21]. Login to comment

PMID: 25861753 [PubMed] Wang ZC et al: "Genetic polymorphisms of the multidrug resistance 1 gene MDR1 and the risk of hepatocellular carcinoma."

No. Sentence Comment

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). Login to comment

PMID: 26535588 [PubMed] Nishijima T et al: "Drug Transporter Genetic Variants Are Not Associated with TDF-Related Renal Dysfunction in Patients with HIV-1 Infection: A Pharmacogenetic Study."

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97 >10 ml/min/1.73 m2 decrement in eGFR from baseline >25% decrement in eGFR from baseline eGFR <60 ml/min/1.73 m2 Amino acid >10 ml/min/ 1.73 m2 decrement (n = 624) No decrement (n = 79) P value* >25% decrement (n = 119) No decrement (n = 584) P value* <60 ml/ min/1.73 m2 (n = 126) No decrement (n = 577) P value* ABCC2 (MRP2) -24 C!T, rs717620 C/C 382 (61) 51 (65) 76 (64) 357 (61) 83 (66) 350 (61) C/T 215 (35) 27 (34) 0.53 38 (32) 204 (35) 0.83 38 (30) 204 (35) 0.51 T/T 27 (4) 1 (1) 5 (4) 23 (4) 5 (4) 23 (4) 1249 G!A, rs2273697 Val417Ile G/G 483 (78) 61 (77) 93 (78) 451 (77) 100 (79) 444 (77) A/G 132 (21) 16 (20) 0.68 24 (20) 124 (21) 0.97 24 (19) 124 (21) 0.81 A/A 9 (1) 2 (3) 2 (2) 9 (2) 2 (2) 9 (2) ABCB1 (P-glycoprotein) 2677T!A/ G, rs2032582 A: Ser893Thr G: Ser893Ala T/T 112 (18) 13 (16) 19 (16) 106 (18) 21 (17) 104 (18) T/A 77 (12) 13 (16) 22 (18) 68 (11) 18 (14) 72 (12) G/G 122 (20) 13 (16) 0.74 20 (17) 115 (20) 0.40 21 (17) 114 (20) 0.94 G/T 195 (31) 29 (37) 39 (33) 185 (32) 41 (32) 183 (32) G/A 96 (15) 9 (12) 17 (14) 88 (15) 20 (16) 85 (15) A/A 22 (4) 2 (3) 2 (2) 22 (4) 5 (4) 19 (3) *By use of Fisher`s exact test for 2&#d7;3 table (2&#d7;6 table for rs2032582). Login to comment
102 >10 ml/min/1.73 m2 decrement in eGFR from baseline >25% decrement in eGFR from baseline eGFR <60 ml/min/1.73 m2 Amino acid >10 ml/min/ 1.73 m2 decrement (n = 624) No decrement (n = 79) P value* >25% decrement (n = 119) No decrement (n = 584) P value* <60 ml/ min/1.73 m2 (n = 126) No decrement (n = 577) P value* ABCC2 (MRP2) -24 C!T, rs717620 C/C 302 (62) 131 (61) 79 (64) 354 (61) 38 (66) 395 (61) C/T 166 (34) 76 (36) 0.59 39 (31) 203 (35) 0.62 18 (31) 224 (35) 0.91 T/T 22 (4) 6 (3) 6 (5) 22 (4) 2 (3) 26 (4) 1249 G!A, rs2273697 Val417Ile G/G 386 (79) 158 (74) 98 (79) 446 (77) 45 (78) 499 (77) A/G 95 (19) 53 (25) 0.20 24 (19) 124 (21) 0.86 12 (21) 136 (21) 1.00 A/A 9 (2) 2 (1) 2 (2) 9 (2) 1 (1) 10 (2) ABCB1 (P-glycoprotein) 2677T!A/ G, rs2032582 A: Ser893Thr G: Ser893Ala T/T 83 (17) 42 (20) 19 (15) 106 (18) 9 (15) 116 (18) T/A 62 (13) 28 (13) 24 (19) 66 (11) 8 (14) 82 (13) G/G 95 (19) 40 (19) 0.95 21 (17) 114 (20) 0.22 12 (21) 123 (19) 0.76 G/T 157 (32) 67 (31) 41 (33) 183 (32) 15 (26) 209 (32) G/A 75 (15) 30 (14) 17 (14) 88 (15) 12 (21) 93 (14) A/A 18 (4) 6 (3) 2 (2) 22 (4) 2 (3) 22 (4) *By use of Fisher`s exact test for 2&#d7;3 table (2&#d7;6 table for rs2032582). Login to comment