ABCMdb

PMID: 18416940

Seo T, Ishitsu T, Oniki K, Abe T, Shuto T, Nakagawa K
ABCC2 haplotype is not associated with drug-resistant epilepsy.
J Pharm Pharmacol. 2008 May;60(5):631-5., [PubMed]

Sentences

No. Mutations Sentence Comment

5 ABCB1 p.Gly1249Ala On the other hand, the delGCGC haplotype at G-1774delG, C-24T, G1249A and C3972T was over represented among the epileptic patients with a complication of mental retardation in comparison with those without (32.4% vs 22.0%; P=0.009); and the G-1774delG allele was also associated with mental retardation (P=0.03). Login to comment 12 ABCB1 p.Gly1249Ala Therefore a linkage disequilibrium analysis was performed to investigate the association between the ABCC2 genotypes of G-1774delG, C-24T, G1249A and C3972T or these haplotypes and clarify the responsiveness to the AED therapy among epileptic patients. Login to comment 34 ABCB1 p.Gly1249Ala ABCC2 polymorphisms at C-24T (rs717620), G1249A (rs2273697) and C3972T (rs3740066) were determined by polymerase chain reaction (PCR)-restriction fragment length polymorphism as reported by Naesens et al (2006) and Rau et al (2006). Login to comment 45 ABCB1 p.Gly1249Ala On the other hand, a significant linkage disequilibrium was detected among G-1774delG, C-24T, G1249A and C3972T (each ⏐D`⏐ > 0.75; P < 0.0001). Login to comment 56 ABCB1 p.Gly1249Ala In this study, the ABCC2 genotypes or haplotypes did not have any impact on the responsiveness to AEDs, while significant associations between mental retardation and the G-1774delG polymorphism or delGCGC haplotype at G-1774delG, C-24T, G1249A and C3972T were observed. Login to comment 67 ABCB1 p.Gly1249Ala Responsive (n = 146) Resistant (n = 133) P value Male 79 (54.1%) 77 (57.9%) 0.55 Age (years) 20.7 ± 11.0 21.1 ± 9.1 0.69 Body weight (kg) 49.1 ± 18.5 46.4 ± 20.4 0.25 Onset of epilepsy (years) 5.8 ± 5.0 3.7 ± 4.6 <0.001 Duration of therapy (years) 8.7 ± 4.4 9.6 ± 4.5 0.09 Mental retardation 72(49.3%) 113 (85.0%) <0.001 Seizure typea Partial 95(65.1%) 95(71.4%) 0.38 Generalized 47(32.2%) 33(24.8%) Aetiology Idiopathic 42(28.8%) 8(6.0%) <0.001 Cryptogenic 66(45.2%) 50(37.6%) Symptomatic 38(26.0%) 75(56.4%) Prescribed AEDsb Carbamazepine 64(43.8%) 76(57.1%) 0.031 Phenytoin 6(4.1%) 19(14.3%) 0.003 Phenobarbital 14(9.6%) 24(18.0%) 0.054 Valproic acid 38(26.0%) 47(35.3%) 0.12 Zonisamide 12(8.2%) 22(16.5%) 0.043 Clobazam 17 (11.6%) 44(33.1%) < 0.001 Table 2 Frequency of ABCC2 genotypes and haplotypes in drug-responsive and -resistant epilepsy a P values were determined by Fisher`s exact test for genotype frequencies and 10 000 permutation test for haplotype frequencies. b Haplotype configuration was defined as G-1774delG, C-24T, G1249A and C3972T. Login to comment 69 ABCB1 p.Gly1249Ala Variant Responsive (n = 146) Resistant (n = 133) P valuea G-1774delG G/G 77(58.8%) 54(41.2%) 0.08 G/delG 58(45.0%) 71(55.0%) delG/delG 11(57.9%) 8(42.1%) C-24T C/C 93(53.1%) 82(46.9%) 0.81 C/T 47(50.0%) 47(50.0%) T/T 6(60.0%) 4(40.0%) G1249A G/G 104(50.5%) 102(49.5%) 0.25 G/A 35(54.7%) 29(45.3%) A/A 7(77.8%) 2(22.2%) C3972T C/C 89(52.0%) 82(48.0%) 0.66 C/T 48(51.1%) 46(48.9%) T/T 9(64.3%) 5(35.7%) Haplotypesb GCGC 33.2% 32.3% 0.83 delGCGC 25.5% 32.7% 0.049 GTGT 17.7% 18.8% 0.73 GCAC 16.2% 12.0% 0.19 Otherc 7.4% 4.2% - 634 Takayuki Seo et al (2007b) indicated that substrate recognition or transport efficacy by efflux transporters differed between man and mouse for certain AEDs. Login to comment 74 ABCB1 p.Gly1249Ala A significant linkage was found among the C-24T, G1249A and C3972T polymorphisms of ABCC2, and the genotypes and haplotypes were reported to influence the expression of ABCC2 mRNA or protein, dispositions of the substrates, and adverse reactions (Naesens et al 2006; Rau et al 2006; de Jong et al 2007; Haenisch et al 2007). Login to comment 95 ABCB1 p.Gly1249Ala Table 3 Frequency of ABCC2 genotypes and haplotypes in mental retardation and non-mental retardation groups a P values were determined by Fisher`s exact test for genotype frequencies and 10000 permutation test for haplotype frequencies. b delG carriers vs non-carriers, P = 0.03. c Haplotype configuration was defined as G-1774delG, C-24T, G1249A and C3972T. Login to comment 97 ABCB1 p.Gly1249Ala Variant Non-mental retardation (n = 94) Mental retardation (n = 185) P valuea G-1774delGb G/G 53(40.5%) 78(59.5%) 0.08 G/delG 36(27.9%) 93(72.1%) delG/delG 5(26.3%) 14(73.7%) C-24T C/C 58(33.1%) 117(66.9%) 0.55 C/T 31(33.0%) 63(67.0%) T/T 5(50.0%) 5(50.0%) G1249A G/G 66(32.0%) 140(68.0%) 0.54 G/A 25(39.1%) 39(60.9%) A/A 3(33.3%) 6(66.7%) C3972T C/C 58(33.9%) 113(66.1%) 0.13 C/T 28(29.8%) 66(70.2%) T/T 8(57.1%) 6(42.9%) Haplotypesc GCGC 35.5% 31.4% 0.34 delGCGC 22.0% 32.4% 0.009 GTGT 17.9% 18.3% 1.00 GCAC 15.2% 13.8% 0.61 Otherd 9.4% 4.1% - 635 Conclusion This study showed that ABCC2 polymorphisms may not have influenced the AED responsiveness. Login to comment