ABCMdb

PMID: 22178260

Kim SH, Kim SH, Lee JH, Lee BH, Kim YS, Park JS, Jee YK
Polymorphisms in drug transporter genes (ABCB1, SLCO1B1 and ABCC2) and hepatitis induced by antituberculosis drugs.
Tuberculosis (Edinb). 2012 Jan;92(1):100-4. Epub 2011 Dec 16., [PubMed]

Sentences

No. Mutations Sentence Comment

48 ABCC2 p.Val417Ile Gene (chromosome) Reference SNP ID Position SNP name Chromosome position (dbSNP build 126) Minor allele frequency HWE p-value ABCB1 (7q21.1) rs10261685 Promoter À114918T > G 86989069 0.408 0.639 rs17149694 Exon 27 T1141S (T > A) 86783310 0.122 1 rs1045642 Exon 27 I1145I (T > C) 86783296 0.119 1 SLCO1B1 (12p12.2) rs4149013 Promoter À12095A > G 24844102 0.202 0.391 rs4149014 Promoter À11556G > T 24844641 0.288 0.799 rs11835045 Promoter À10690C > T 24845507 0.071 1 rs2306283 Exon 5 D130N (G > A) 24891397 0.195 0.929 rs4149056 Exon 6 A174V (T > C) 24893202 0.155 0.463 ABCC2 (10q24) Novel Promoter À1774del > G 101672054 0.381 1 rs1885301 Promoter À1549G > A 101672279 0.293 1 rs717620 Promoter À24C > T 101673804 0.267 0.399 rs2804400 Intron IVS3-49C > T 101684485 0.290 1 rs2273697 Exon 10 V417I (G > A) 101695041 0.066 0.580 rs3740070 Exon 22 S978S (G > A) 101722644 0.050 0.436 rs3740066 Exon 28 I1324I (C > T) 101735433 0.292 0.503 Polymorphisms selected for genotyping are indicated in bold. Login to comment 56 ABCC2 p.Val417Ile Of the 12 SNPs screened in ABCC2, seven SNPs (À1774del > G, À1549G > A, À24C > T, IVS3-49C > T, V417I G > A, S978S G > A, I1324I C > T) had a frequency >2.0% in healthy subjects and were genotyped in our study subjects. Login to comment 72 ABCC2 p.Val417Ile Gene SNP Genotype Hepatitis (N ¼ 67) Control (N ¼ 159) P value ABCB1 À114918T > G TT 56 (72.2%) 130 (81.8%) NS TG 9 (22.2%) 29 (18.2%) GG 1 (5.6%) 0 (0.0%) I1145I CC 27 (40.9%) 68 (42.9%) NS CT 31 (47.0%) 69 (41.8%) TT 8 (12.1%) 20 (15.3%) SLCO1B1 À12095A > G AA 43 (65.2%) 115 (74.2%) NS AG 23 (34.8%) 35 (22.6%) GG 0 (0.0%) 5 (3.2%) À11556G > T TT 38 (57.6%) 83 (53.2%) NS TG 23 (34.9%) 64 (41.0%) GG 5 (7.6%) 9 (5.8%) D130N GG 33 (50.8%) 85 (54.5%) NS GA 26 (40.0%) 60 (38.5%) AA 6 (9.2%) 11 (7.0%) A174V TT 46 (69.7%) 113 (72.4%) NS TC 20 (30.3%) 40 (25.6%) CC 0 (0.0%) 3 (1.9%) ABCC2 À1774del > G GG 25 (37.9%) 43 (27.4%) NS G/- 33 (50.0%) 94 (59.9%) À/À 8 (12.1%) 20 (12.7%) À1549G > A GG 34 (51.5%) 89 (57.1%) NS GA 27 (40.9%) 60 (38.5%) AA 5 (7.6%) 7 (4.5%) À24C > T CC 38 (52.6%) 92 (59.4%) NS CT 26 (39.4%) 57 (36.8%) TT 2 (3.0%) 6 (3.9%) IVS3-49C > T CC 34 (50.8%) 91 (57.2%) NS CT 29 (43.3%) 61 (38.4%) TT 4 (6.0%) 7 (4.4%) V417I GG 61 (92.4%) 134 (84.3%) NS GA 5 (7.6%) 23 (14.5%) AA 0 (0.0%) 2 (1.3%) S978S GG 61 (92.4%) 147 (92.5%) NS GA 5 (7.6%) 12 (7.6%) AA 0 (0.0%) 0 (0.0%) I1324I CC 35 (53.0%) 91 (58.3%) NS CT 26 (39.4%) 56 (35.9%) TT 5 (7.6%) 9 (5.8%) NS, not significant. Login to comment 77 ABCB11 p.Val444Ala Previous studies revealed that hepatocellular-type hepatitis was associated with ABCC2 À24C > T polymorphism, whereas cholestatic-type was associated with the ABCB11 V444A and ABCC2 À1774delG variation.13,15,24 In this study, we focused on just ATD-induced hepatitis, instead of various DILIs, and the DILI patterns were hepatocellular in all cases. Login to comment