ABCC2 p.Ile1324Ser
| ClinVar: |
c.3972C>T
,
p.Ile1324=
N
, Benign
|
| Predicted by SNAP2: | A: D (59%), C: N (53%), D: D (85%), E: D (80%), F: D (53%), G: D (80%), H: D (75%), K: D (85%), L: N (57%), M: D (53%), N: D (80%), P: D (85%), Q: D (75%), R: D (85%), S: D (71%), T: D (63%), V: N (93%), W: D (80%), Y: D (71%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: D, G: D, H: D, K: D, L: N, 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] MDR-1 and MRP2 Gene Polymorphisms in Mexican Epile... Front Neurol. 2014 Oct 9;5:184. doi: 10.3389/fneur.2014.00184. eCollection 2014. Escalante-Santiago D, Feria-Romero IA, Ribas-Aparicio RM, Rayo-Mares D, Fagiolino P, Vazquez M, Escamilla-Nunez C, Grijalva-Otero I, Lopez-Garcia MA, Orozco-Suarez S
MDR-1 and MRP2 Gene Polymorphisms in Mexican Epileptic Pediatric Patients with Complex Partial Seizures.
Front Neurol. 2014 Oct 9;5:184. doi: 10.3389/fneur.2014.00184. eCollection 2014., [PMID:25346718]
Abstract [show]
Although the Pgp efflux transport protein is overexpressed in resected tissue of patients with epilepsy, the presence of polymorphisms in MDR1/ABCB1 and MRP2/ABCC2 in patients with antiepileptic-drugs resistant epilepsy (ADR) is controversial. The aim of this study was to perform an exploratory study to identify nucleotide changes and search new and reported mutations in patients with ADR and patients with good response (CTR) to antiepileptic drugs (AEDs) in a rigorously selected population. We analyzed 22 samples In Material and Methods, from drug-resistant patients with epilepsy and 7 samples from patients with good response to AEDs. Genomic DNA was obtained from leukocytes. Eleven exons in both genes were genotyped. The concentration of drugs in saliva and plasma was determined. The concentration of valproic acid in saliva was lower in ADR than in CRT. In ABCB1, five reported SNPs and five unreported nucleotide changes were identified; rs2229109 (GA) and rs2032582 (AT and AG) were found only in the ADR. Of six SNPs associated with the ABCC2 that were found in the study population, rs3740066 (TT) and 66744T > A (TG) were found only in the ADR. The strongest risk factor in the ABCB1 gene was identified as the TA genotype of rs2032582, whereas for the ABCC2 gene the strongest risk factor was the T allele of rs3740066. The screening of SNPs in ACBC1 and ABCC2 indicates that the Mexican patients with epilepsy in this study display frequently reported ABCC1 polymorphisms; however, in the study subjects with a higher risk factor for drug resistance, new nucleotide changes were found in the ABCC2 gene. Thus, the population of Mexican patients with AED-resistant epilepsy (ADR) used in this study exhibits genetic variability with respect to those reported in other study populations; however, it is necessary to explore this polymorphism in a larger population of patients with ADR.
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No. Sentence Comment
95 The AGT and AGC triplets produce an amino acid change (Ile1324Ser, Figure 1A); these occur Table 3 | Genotype and allelic relative frequencies of SNPs, MAF value, amino acid changes, and OR found in ABCB1 and ABCC2 genes. Gene SNP Sample Allele frequency Genotype frequency MAF Protein association Odds ratio aa, change Localization Allele Genotype Heterozogous Homozygous ABCB1 rs2214102 CTR G = 1.000 G/G = 1.000 A = 0.040/88 50UTR region [G] [A], 2.446 [GG] [GA], 2.692 [GG] [AA], 0.385 ADR G = 0.971 G/G = 0.955 A = 0.029 G/A = 0.045 rs2229109 CTR G = 1.000 G/G = 1.000 A = 0.017/36 400; G >A; Ser >Asn Cytoplasmatic; binding site; Second domain [G] [A], 1.706 [GG] [GA], 1.829 [GG] [AA], 0.366 ADR G = 0.955 G/G = 0.909 A = 0.045 G/A = 0.091 rs1128503 CTR T = 0.571 C/T = 0.571 T = 0.422/919 412; T > C; Gly > Gly Cytoplasmatic; beta chain; second domain [T] [C], 1.543 [TT] [TC], 1.200 [TT] [CC], 3.000 C = 0.429 T/T = 0.286 C/C = 0.143 ADR T = 0.455 C/T = 0.545 C = 0.545 T/T = 0.182 C/C = 0.273 rs2032582 CTR G = 0.500 G/T = 0.429 A = 0.340/741 893; T >A; Ser >Thr Cytoplasmatic; Alfa-helix chain; third domain [T] [A], 2.143 [TT] [TA], 2.778 [TT] [AA], 0.526 T = 0.500 G/G = 0.286 893; T > G; Ser >Ala T/T = 0.286 [T] [G], 1.375 [TT] [TG], 1.333 [TT] [GG], 1.750 ADR G = 0.523 G/T = 0.364 T = 0.409 G/G = 0.318 A = 0.068 T/T = 0.182 A/G = 0.045 A/T = 0.091 rs1045642 CTR T = 0.429 TT = 0.143 T = 0.397/864 1145; T > C Ile > Ile Cytoplasmatic, fourth domain [T] [C], 0.825 [TT] [TC], 0.500 [TT] [CC], 0.600 C = 0.571 TC = 0.571 CC = 0.286 ADR T = 0.475 TT = 0.255 C = 0.525 TC = 0.450 CC = 0.300 rs2235047 CTR T = 0.857 TT = 0.714 G = 0.179/389 Intron between 25 and 26 exon [T] [G], 1.020 [TT] [TG], 1.026 [TT] [GG], 0.407 G = 0.143 TG = 0.286 ADR T = 0.800 TT = 0.600 G = 0.200 TG = 0.400 (Continued) Table 3 | Continued Gene SNP Sample Allele frequency Genotype frequency MAF Protein association Odds ratio aa, change Localization Allele Genotype Heterozogous Homozygous rs2235048 CTR C = 0.429 CC = 0.143 C = 0.398/867 Intron between 25 and 26 exon [C] [T], 0.682 [CC] [CT], 0.417 [CC] [TT], 0.417 T = 0.571 CT = 0.571 TT = 0.286 ADR C = 0.525 CC = 0.300 T = 0.472 CT = 0.450 TT = 0.250 ABCC2 66744 T > G CTR T = 1.000 T/T = 1.000 No reported 1323; T > G; Ile > Ser Cytoplasmatic region, fourth domain [T] [G], 4.038 [TT] [TG], 4.1714 [TT] [GG], 0.429 ADR T = 0.890 T/T = 0.770 G = 0.110 T/A = 0.230 rs3740066 CTR C = 0.928 C/C = 0.857 T = 0.304/663 1324; C >T; Ile > Ile Cytoplasmatic region, fourth domain [C] [T], 4.875 [CC] [CT], 2.769 [CC] [TT], 3.370 T = 0.072 C/T = 0.143 ADR C = 0.727 C/C = 0.591 T = 0.273 C/T = 0.273 T/T = 0.136 68049 T >A CTR T = 0.790 TT = 0.570 No reported 1373; T >A; Leu > His Cytoplasmatic region, fourth domain [T] [A], 0.733 [TT] [TA], 0.667 [TT] [AA], 0.310 A = 0.210 TA = 0.430 ADR T = 0.840 TT = 0.680 A = 0.160 TA = 0.320 67967C >A CTR C = 0.500 CA = 1.000 No reported 1342; C >A; Ser > Ser Cytoplasmatic region, fourth domain [C] [A], 0.760 [CC] [CA], 0.371 [CC] [AA], 0.143 A = 0.500 ADR C = 0.570 CC = 0.140 A = 0.430 CA = 0.860 68072C >A CTR C = 0.500 CA = 1.000 No reported 1381; C >A; Pro >Thr Cytoplasmatic region, fourth domain [C] [A], 0.750 [CC] [CA], 0.352 [CC] [AA], 0.143 A = 0.500 ADR C = 0.590 CC = 0.180 A = 0.410 CA = 0.820 68088 G > C CTR G = 0.710 GG = 0.710 No reported Intron between 29 and 30 [G] [C], 0.147 [GG] [GC], 0.314 [GG] [CC], 0.147 C = 0.290 CC = 0.290 ADR G = 0.890 GG = 0.840 C = 0.110 CC = 0.160 Relative frequencies are presented for the five SNPs reported on NCBI Gene Bank database of ABCB1 and ABCC2 genes among 14 controlled and 44 drug-resistant patients (2n), obtained by direct sequencing.
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ABCC2 p.Ile1324Ser 25346718:95:55
status: NEW96 The AGT and AGC triplets produce an amino acid change (Ile1324Ser, Figure 1A); these occur Table 3 | Genotype and allelic relative frequencies of SNPs, MAF value, amino acid changes, and OR found in ABCB1 and ABCC2 genes. Gene SNP Sample Allele frequency Genotype frequency MAF Protein association Odds ratio aa, change Localization Allele Genotype Heterozogous Homozygous ABCB1 rs2214102 CTR G = 1.000 G/G = 1.000 A = 0.040/88 50UTR region [G] [A], 2.446 [GG] [GA], 2.692 [GG] [AA], 0.385 ADR G = 0.971 G/G = 0.955 A = 0.029 G/A = 0.045 rs2229109 CTR G = 1.000 G/G = 1.000 A = 0.017/36 400; G >A; Ser >Asn Cytoplasmatic; binding site; Second domain [G] [A], 1.706 [GG] [GA], 1.829 [GG] [AA], 0.366 ADR G = 0.955 G/G = 0.909 A = 0.045 G/A = 0.091 rs1128503 CTR T = 0.571 C/T = 0.571 T = 0.422/919 412; T > C; Gly > Gly Cytoplasmatic; beta chain; second domain [T] [C], 1.543 [TT] [TC], 1.200 [TT] [CC], 3.000 C = 0.429 T/T = 0.286 C/C = 0.143 ADR T = 0.455 C/T = 0.545 C = 0.545 T/T = 0.182 C/C = 0.273 rs2032582 CTR G = 0.500 G/T = 0.429 A = 0.340/741 893; T >A; Ser >Thr Cytoplasmatic; Alfa-helix chain; third domain [T] [A], 2.143 [TT] [TA], 2.778 [TT] [AA], 0.526 T = 0.500 G/G = 0.286 893; T > G; Ser >Ala T/T = 0.286 [T] [G], 1.375 [TT] [TG], 1.333 [TT] [GG], 1.750 ADR G = 0.523 G/T = 0.364 T = 0.409 G/G = 0.318 A = 0.068 T/T = 0.182 A/G = 0.045 A/T = 0.091 rs1045642 CTR T = 0.429 TT = 0.143 T = 0.397/864 1145; T > C Ile > Ile Cytoplasmatic, fourth domain [T] [C], 0.825 [TT] [TC], 0.500 [TT] [CC], 0.600 C = 0.571 TC = 0.571 CC = 0.286 ADR T = 0.475 TT = 0.255 C = 0.525 TC = 0.450 CC = 0.300 rs2235047 CTR T = 0.857 TT = 0.714 G = 0.179/389 Intron between 25 and 26 exon [T] [G], 1.020 [TT] [TG], 1.026 [TT] [GG], 0.407 G = 0.143 TG = 0.286 ADR T = 0.800 TT = 0.600 G = 0.200 TG = 0.400 (Continued) Table 3 | Continued Gene SNP Sample Allele frequency Genotype frequency MAF Protein association Odds ratio aa, change Localization Allele Genotype Heterozogous Homozygous rs2235048 CTR C = 0.429 CC = 0.143 C = 0.398/867 Intron between 25 and 26 exon [C] [T], 0.682 [CC] [CT], 0.417 [CC] [TT], 0.417 T = 0.571 CT = 0.571 TT = 0.286 ADR C = 0.525 CC = 0.300 T = 0.472 CT = 0.450 TT = 0.250 ABCC2 66744 T > G CTR T = 1.000 T/T = 1.000 No reported 1323; T > G; Ile > Ser Cytoplasmatic region, fourth domain [T] [G], 4.038 [TT] [TG], 4.1714 [TT] [GG], 0.429 ADR T = 0.890 T/T = 0.770 G = 0.110 T/A = 0.230 rs3740066 CTR C = 0.928 C/C = 0.857 T = 0.304/663 1324; C >T; Ile > Ile Cytoplasmatic region, fourth domain [C] [T], 4.875 [CC] [CT], 2.769 [CC] [TT], 3.370 T = 0.072 C/T = 0.143 ADR C = 0.727 C/C = 0.591 T = 0.273 C/T = 0.273 T/T = 0.136 68049 T >A CTR T = 0.790 TT = 0.570 No reported 1373; T >A; Leu > His Cytoplasmatic region, fourth domain [T] [A], 0.733 [TT] [TA], 0.667 [TT] [AA], 0.310 A = 0.210 TA = 0.430 ADR T = 0.840 TT = 0.680 A = 0.160 TA = 0.320 67967C >A CTR C = 0.500 CA = 1.000 No reported 1342; C >A; Ser > Ser Cytoplasmatic region, fourth domain [C] [A], 0.760 [CC] [CA], 0.371 [CC] [AA], 0.143 A = 0.500 ADR C = 0.570 CC = 0.140 A = 0.430 CA = 0.860 68072C >A CTR C = 0.500 CA = 1.000 No reported 1381; C >A; Pro >Thr Cytoplasmatic region, fourth domain [C] [A], 0.750 [CC] [CA], 0.352 [CC] [AA], 0.143 A = 0.500 ADR C = 0.590 CC = 0.180 A = 0.410 CA = 0.820 68088 G > C CTR G = 0.710 GG = 0.710 No reported Intron between 29 and 30 [G] [C], 0.147 [GG] [GC], 0.314 [GG] [CC], 0.147 C = 0.290 CC = 0.290 ADR G = 0.890 GG = 0.840 C = 0.110 CC = 0.160 Relative frequencies are presented for the five SNPs reported on NCBI Gene Bank database of ABCB1 and ABCC2 genes among 14 controlled and 44 drug-resistant patients (2n), obtained by direct sequencing.
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ABCC2 p.Ile1324Ser 25346718:96:55
status: NEW