ABCMdb

PMID: 25630984

Birmingham BK, Bujac SR, Elsby R, Azumaya CT, Zalikowski J, Chen Y, Kim K, Ambrose HJ
Rosuvastatin pharmacokinetics and pharmacogenetics in Caucasian and Asian subjects residing in the United States.
Eur J Clin Pharmacol. 2015 Mar;71(3):329-40. doi: 10.1007/s00228-014-1800-0. Epub 2015 Jan 30., [PubMed]

Sentences

No. Mutations Sentence Comment

4 ABCG2 p.Gln141Lys The influence of polymorphisms in SLCO1B1 (T521>C [Val174Ala] and A388>G [Asn130Asp]) and in ABCG2 (C421>A [Gln141Lys]) on exposure to rosuvastatin was also assessed. Login to comment 37 ABCG2 p.Gln141Lys In addition, an exploratory pharmacogenetic analysis was performed to examine the effects of three SNPs on rosuvastatin pharmacokinetics, including two polymorphisms in SLCO1B1 (T521>C [Val174Ala] and A388>G [Asn130Asp]) and one polymorphism in ABCG2 (C421>A [Gln141Lys]). Login to comment 62 ABCG2 p.Gln141Lys All data were analyzed with Sequence Detection Systems (c) software v2.1: SLCO1B1 A388G (Asn130Asp) rs2306283 and ABI assay C__1901697_20 SLCO1B1 T521C (Val174Ala) rs4149056 and ABI assay C__30633906_10 ABCG2 C421A (Gln141Lys) rs2231142 and ABI assay C__15854163_70. Login to comment 133 ABCG2 p.Gln141Lys The 421A allele, present at a higher frequency in the Asian populations (apart from the Asian Indians) than in the Caucasian population (Table 4), appeared to account Table 4 Genotype frequencies and HWE results by ethnic group Polymorphism Genotype Frequency (%) Pooled Asiana n=100 Chinese n=17 Filipino n=19 Asian-Indian n=16 Korean n=23 Vietnamese n=16 Japanese n=25 Caucasian n=22 SLCO1B1: T521>C (Val174Ala) T\T T\C C\C 78 (78 %) 22 (22 %) 0 15 (88 %) 2 (12 %) 0 14 (74 %) 5 (26 %) 0 16 (100 %) 0 0 18 (78 %) 5 (22 %) 0 12 (75 %) 4 (25 %) 0 19 (76 %) 6 (24 %) 0 15 (68 %) 6 (27 %) 1 (5 %) HWE p value - 1.00 1.00 1.00 1.00 1.00 1.00 0.54 SLCO1B1: A388>G (Asn130Asp) A\A A\G G\G 7 (7 %) 33 (33 %) 60 (60 %) 1 (6 %) 5 (29 %) 11 (65 %) 2 (11 %) 2 (11 %) 15 (79 %) 4 (25 %) 8 (50 %) 4 (25 %) 2 (9 %) 11 (48 %) 10 (43 %) 0 (0 %) 2 (12.5 %) 14 (87.5 %) 2 (8 %) 13 (52 %) 10 (40 %) 9 (41 %) 9 (41 %) 4 (18 %) HWE p value - 0.54 0.03 1.00 1.00 1.00 0.66 0.65 ABCG2: C421>A (Gln141Lys) C\C C\A A\A 49 (49 %) 46 (46 %) 5 (5 %) 7 (41 %) 10 (59 %) 0 10 (53 %) 7 (37 %) 2 (11 %) 14 (88 %) 1 (6 %) 1 (6 %) 13 (57 %) 10 (43 %) 0 7 (44 %) 8 (50 %) 1 (6 %) 12 (48 %) 11 (44 %) 2 (8 %) 15 (68 %) 7 (32 %) 0 HWE p value - 0.24 0.61 0.10 0.54 1.00 1.00 1.00 HWE Hardy-Weinberg equilibrium a The pooled Asian group comprised all Chinese, Filipino, Korean, Vietnamese and Japanese subjects for some but not all of the inter-ethnic group variability in exposure. Login to comment 199 ABCG2 p.Gln141Lys A study in Chinese subjects investigating the effect of the ABCG2 C421>A (Gln141Lys) polymorphism on rosuvastatin exposure has suggested that the 421A allele is significantly associated with higher Cmax and AUC than the 421C allele [15]. Login to comment