ABCMdb

PMID: 23940561

Chen WQ, Shu Y, Li Q, Xu LY, Roederer MW, Fan L, Wu LX, He FZ, Luo JQ, Tan ZR, He YJ, Zhou HH, Chen X, Zhang W
Polymorphism of ORM1 is associated with the pharmacokinetics of telmisartan.
PLoS One. 2013 Aug 5;8(8):e70341. doi: 10.1371/journal.pone.0070341. Print 2013., [PubMed]

Sentences

No. Mutations Sentence Comment

39 ABCB1 p.Gly1249Ala ABCC2 was highly polymorphic, and it was reported that three common SNPs C-24T, G1249A and C3972T [19,25] were in linkage disequilibrium and likes to decrease the transporter function probably by a posttranscriptional modification on transporter protein expression [19,20]. Login to comment 77 ABCB1 p.Gly1249Ala The genotypes of ABCC2 C3972T, ABCC2 G1249A, and, SLCO1B3 T334G were determined by a PCR-RFLP procedure as described in previous reports. Login to comment 79 ABCB1 p.Gly1249Ala The primers for ABCC2 G1249A were 59-GGGCAAAGAAGTGTGTGGAT-39 (Forward) and 59-TGGGATTACAAGCACCATCA-39 (Reversed) and the endonuclease enzyme was NcoI. Login to comment 81 ABCB1 p.Gly1249Ala The Linkage Disequilibrium Analysis The linkage disequilibrium analysis of the ABCC2 variants (C-24T, G1249A and C3972T) was constructed using the online software SHEsis (http://analysis2.bio-x.cn/my Analysis.php). Login to comment 107 ABCB1 p.Gly1249Ala The linkage disequilibrium among the ABCC2 single nucleotide polymorphisms (SNPs) was analyzed, and the results showed that the alleles of ABCC2 C3972T was mostly in a linkage with ABCC2 C-24T (D9 = 0.997, r2 = 0.031), and the D9 value was 0.793 and r2 = 0.606 when the analysis tested between the SNPs of ABCC2 G1249A and C-24T. Login to comment 123 ABCB1 p.Gly1249Ala In this study, the polymorphisms of ABCC2(G1249A), ABCB1 (C3435T), SLCO1B3 (T334G) and ABCG2 (C421A) had no significant influence on the PKs of telmisartan and the BP change(%) from the baseline after taking telmisartan (Table 3, 4, 5). Login to comment 139 ABCB1 p.Gly1249Ala Nucleotide substitution Location Amino Acids MAFa (CHB) MAFa (ASW) MAFa (CEU) MAFb (CHB) ORM1 rs17650 A113G Exon Gln/Arg 0.275[37] N/A N/A 0.208 ABCC2 rs717620 C-24T 59UTR - 0.201 0.035 0.181 0.281 rs3740066 C3972T Exon Ile/Ile 0.267 0.331 N/A 0.250 rs2273697 G1249A Exon Val/Ile 0.106 0.243 0.132 0.083 ABCB1 rs1045642 C3435T Exon Ile/Ile 0.374 0.205 0.571 0.375 SLCO1B3 rs4149117 T334G Exon Ala/Ser 0.266 0.518 0.143 0.354 ABCG2 rs2231142 C421A Exon Gln/Lys 0.292 0.044 0.111 0.219 a data published on hapmap; b, data calculated in this study, N = 48; N/A, no data found in hapmap. Login to comment 153 ABCB1 p.Gly1249Ala On the one hand, as ABCC2 C-24T, C3972T, and G1249A SNPs were in a strong linkage disequilibrium, thus the other two SNPs might interfere with C3972T to affect the variability of PKs/PDs. Login to comment 177 ABCB1 p.Gly1249Ala Gene SNPs Genotype AUC(0-48)(ng?h/ml) AUC(0-') (ng?h/ml) Cmax(ng/ml) CL/F(l/h) T1/2 (h) ORM1 A113G AA (28) 1,549.186859.84 1,753.1361,060.60 246.876156.93 32.38621.43 15.6365.09 AG (20) 2,313.5461,257.71 2,686.9061,401.87 293.006184.06 18.6368.74 20.01612.81 P VALUE 0.033* 0.016* 0.289 0.355 0.113 ABCC2 C3972T CC (26) 1,871.186817.89 2,090.836952.69 313.326172.05 18.80610.32 15.8364.11 CT (20) 1,289.896506.60 1,526.476626.97 176.486106.47 10.5966.39 20.09613.27 TT (2) 1,973.906135.44 2,057.50697.27 548.22612.93 32.8960.78 12.2663.11 P VALUE 0.031* 0.105 0.001** 0.001** 0.321 CC vs. CT 0.035* 0.105 0.005** 0.008** 0.476 CC vs.TT 0.896 0.964 0.243 0.083 0.237 CT vs. TT 0.311 0.526 0.014* 0.004** 0.147 ABCC2 C-24T CC (24) 1,809.426843.05 2,017.046976.09 306.166182.01 18.37610.92 15.6164.19 CT (21) 1,348.936525.05 1,588.646637.52 191.526112.96 25.10610.75 19.98612.95 TT (3) 2,214.176427.04 2,411.886617.65 467.576139.99 17.2463.89 14.6264.65 P VALUE 0.060 0.161 0.008** 0.005** 0.523 ABCC2 G1249A GG(41) 1597.796667.24 1832.016790.09 256.456156.87 15.3969.41 18.0169.84 GA(6)+AA(1) 1998.4461108.08 1232.576992.12 355.016236.12 21.30614.17 14.0964.01 P VALUE 0.285 0.417 0.296 0.296 0.614 ABCG2 C421A CC (30) 1,579.226713.71 1,800.866797.05 258.146165.95 15.4969.96 17.69610.97 CA (15) 1,679.296719.04 1,840.076798.27 297.906170.29 17.87610.22 16.34611.36 AA (3) 1,943.436921.94 2,459.6861,394.14 186.586133.13 19.5768.94 20.7565.44 P Value 0.669 0.573 0.481 0.540 0.265 ABCB1 C3435T CC (20) 1,606.836646.33 1,791.716814.66 237.236126.55 14.2367.59 15.4865.05 CT (20) 1,673.536789.53 1,920.076849.29 291.526206.17 17.49612.37 18.95612.29 TT (8) 1,598.626913.64 1,846.3061,026.48 274.706165.31 16.4869.92 18.6768.88 P VALUE 0.587 0.317 0.951 0.984 0.076 SLCO1B3 T334G GG (18) 1,702.256740.60 1,877.336806.34 298.076204.22 17.88612.25 15.9064.08 GT (26) 1,574.476755.06 1,829.076896.92 232.816132.75 13.9767.97 18.56611.78 TT (4) 1,704.896797.20 1,914.586939.86 338.566196.27 25.38613.32 17.3168.43 P VALUE 0.793 0.929 0.424 0.307 0.994 Data were shown as mean6SD; *P,0.05; **P,0.01. Login to comment 181 ABCB1 p.Gly1249Ala SBP change (%) from the baseline DBP change (%) from the baseline Mauchly`s Time Time*genotype genotype Mauchly`s Time Time*genotype genotype ORM1 A113G 0.004 0.000 0.748 0.770 0.000 0.000 0.258 0.096 ABCC2 C3972T 0.006 0.000 0.262 0.162 0.000 0.000 0.067 0.018* ABCC2 G1249A 0.005 0.000 0.795 0.370 0.000 0.030 0.975 0.144 SLCO1B3 T334G 0.001 0.000 0.842 0.995 0.000 0.000 0.431 0.634 ABCG2 C421A 0.001 0.000 0.300 0.255 0.000 0.000 0.451 0.896 ABCB1 C3435T 0.001 0.000 0.369 0.375 0.000 0.000 0.372 0.241 *P,0.05; ORM1, orosomucoid 1; ABCC2, ATP-binding cassette, sub-family C, member 2; SBP, systolic blood pressure; DBP, diastolic blood pressure; Time, the time point in this study including 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 24, 48 h after taking telmisartan. Login to comment 185 ABCB1 p.Gly1249Ala As shown in Table 2, the MAF of ABCC2 C3972T and G1249A, ABCB1 C3435T, SLCO1B3 T334G almost be similar in three main populations. Login to comment