ライフサイエンスコーパス: SLCO1B1

1 rmacokinetic pharmacogenes (CYP2C19, CYP2D6, SLCO1B1).

2 evidence of a role for allelic variation in SLCO1B1.

3 n the organic anion transporter polypeptide, SLCO1B1.

4 pe alleles (n = 10), SLCO1B1*1b/*1b (n = 8), SLCO1B1*15/*15 (n = 7), SLCO1B1*5/*15 (n = 1), SLCO1B1*1

5 CO1B1*15/*15 (n = 7), SLCO1B1*5/*15 (n = 1), SLCO1B1*1a/*5 (n = 6), and SLCO1B3*4/*4 (n = 4) by using

6 explained by UGT1A1*93, ABCC1 IVS11 -48C>T, SLCO1B1*1b, ANC baseline levels, sex, and race (P < .000

7 s of SLCO1B1/1B3 wild-type alleles (n = 10), SLCO1B1*1b/*1b (n = 8), SLCO1B1*15/*15 (n = 7), SLCO1B1*

8 cid were evaluated in 36 healthy carriers of SLCO1B1/1B3 wild-type alleles (n = 10), SLCO1B1*1b/*1b (

9 in certain groups by previous studies, e.g., SLCO1B1(*)31 in the Afro-Caribbean (3.0%) and Sub-Sahara

10 pair statin metabolism; the reduced function SLCO1B1*5 allele impairs statin clearance and is associa

11 SLCO1B1*5 genotype and female sex were associated mild s

12 SLCO1B1*5 was associated with CAE (percent with > or = 1

13 he curve (AUC) is explained by ABCC2 -24C>T, SLCO1B1*5, HNF1A 79A>C, age, and CPT-11 dose (P < .0001)

14 O1B1*1b/*1b (n = 8), SLCO1B1*15/*15 (n = 7), SLCO1B1*5/*15 (n = 1), SLCO1B1*1a/*5 (n = 6), and SLCO1B

15 nucleotide polymorphisms (SNPs) in the NAT2, SLCO1B1, AADAC, and AOX1 loci were genotyped using real-

16 n to be strongly associated with ASD such as SLCO1B1, ACADSB, TCF4, HCP5, MOCOS, SRD5A2, MCCC2, DCC,

17 In candidate analysis, SNPs in SLCO1B1 and LDLR were confirmed as associated with LDL-C

18 nt of statin response, with the exception of SLCO1B1 and risk of myopathy.

19 observed between p.Val174Ala (rs4149056) in SLCO1B1 and SAMS (odds ratio [95% CI], 1.03 [0.90-1.18];

20 between the p.Val174Ala missense variant in SLCO1B1 and SAMS in simvastatin-treated subjects; howeve

21 equenced CYP2D6, CYP2C8, CYP2C9, CYP3A4, and SLCO1B1 and tested 7 reduced function alleles for associ

22 enome-wide significance level (APOE, LPA and SLCO1B1) and a novel rare variant association in GIMAP5

23 clopidogrel (CYP2C19), statins (ABCG2/CYP2C9/SLCO1B1), and NSAIDs (CYP2C9), for which sufficient data

24 n pump inhibitors with CYP2C19, statins with SLCO1B1, and clopidogrel with CYP2C19.

25 s, while some pharmacogenes (i.e. CYP2C9 and SLCO1B1) are modestly associated with persistence, but n

26 n a multivariate analysis including TPMT and SLCO1B1 as covariates, consistent with its influence on

27 on study of children with ALL, we identified SLCO1B1 as harboring multiple common polymorphisms assoc

28 yet heretofore low-priority candidate gene, SLCO1B1, as important determinants of methotrexate's pha

29 orvastatin concentration was associated with SLCO1B1 c.388A>G (P<0.01) and c.521T>C (P<0.05) and 4bet

30 x, ethnicity, dose, and time from last dose, SLCO1B1 c.521T>C (P<0.001) and ABCG2 c.421C>A (P<0.01) w

31 tested the hypothesis that rare variants in SLCO1B1 could affect methotrexate clearance and compared

32 From deep resequencing of SLCO1B1 exons in 699 children, we identified 93 SNPs, 15

33 The top variants in UGT1A1 and SLCO1B1 explain approximately 18.0 and approximately 1.0

34 lded a single nucleotide polymorphism in the SLCO1B1 gene for the organic anion-transporting polypept

35 However, knowledge of SLCO1B1 genotypes is believed to have clinical utility f

36 We verified lower function in vitro of four SLCO1B1 haplotypes that were associated with reduced met

37 ease processes, and the roles for UGT1A1 and SLCO1B1 in drug metabolism, these genetic findings have

38 ed ten genes (DUSP13, KCNJ11, CD300LF/RAB37, SLCO1B1, LRRFIP1, QSER1, UBR2, MOB3C, MST1R, and ABCC8)

39 nd identify two loci, SORT1/CELSR2/PSRC1 and SLCO1B1, not previously identified in GWAS.

40 phisms in the organic anion transporter gene SLCO1B1 (P = 2.1 x 10(-11)).

41 Two SNPs in SLCO1B1, rs11045879 (P = 1.7 x 10(-10)) and rs4149081 (P

42 A previously described SNP in SLCO1B1 (rs4149032) was present at an allele frequency o

43 e (AUC)0-48h increased by 26% (P < .001) per SLCO1B1 rs4149056 C allele.

44 The SLCO1B1 rs4149056 variant was significantly associated w

45 e 12p12.2 region was a non-synonymous SNP in SLCO1B1 (rs4149056, P = 6.7 x 10(-13)), which gives rise

46 re damaging NS variants constituted 17.8% of SLCO1B1's effects (1.9% of total variation) and had larg

47 earance: SLC10A1, SLC22A1, SLC22A7, SLC47A1, SLCO1B1, SLCO1B3, SLCO2B1, ABCB1, ABCB11, ABCC2, ABCC3,

48 e association of methotrexate clearance with SLCO1B1 SNP rs4149056.

49 Further exploration of the impact of SLCO1B1 SNPs on RIF PK is required in this and other pop

50 ients (P = .018 and P = .017), as were other SLCO1B1 SNPs residing in different LD blocks.

51 ) = 1) and with a functional polymorphism in SLCO1B1, T521C (rs4149056; r(2) > 0.84).

52 OATP1B1 (SLCO1B1), the prototypic OATP family member, is the most

53 enotypes for the top UGT1A1 variant, the top SLCO1B1 variant remained highly significant (P = 7.3 x 1

54 or other genetic and non-genetic covariates, SLCO1B1 variants accounted for 10.7% of the population v

55 SNPs in SLCO1B1 were also associated with GI toxicity (odds rati

56 gallstones, top bilirubin SNPs in UGT1A1 and SLCO1B1 were not associated.

57 icance of variants modulating toxicity (e.g. SLCO1B1 with simvastatin) has also been confirmed.