High plasma pravastatin concentrations are associated with single nucleotide polymorphisms and haplotypes of organic anion transporting polypeptide-C (OATP-C, SLCO1B1).

@article{Niemi2004HighPP,
  title={High plasma pravastatin concentrations are associated with single nucleotide polymorphisms and haplotypes of organic anion transporting polypeptide-C (OATP-C, SLCO1B1).},
  author={Mikko Niemi and Elke Schaeffeler and Thomas Lang and Martin F. Fromm and Mikko Neuvonen and Carl Kyrklund and Janne T. Backman and Reinhold Kerb and Matthias Schwab and Pertti J. Neuvonen and Michel F Eichelbaum and Kari T. Kivistö},
  journal={Pharmacogenetics},
  year={2004},
  volume={14 7},
  pages={
          429-40
        }
}
This study aimed to characterize possible relationships between polymorphisms in the drug transporter genes organic anion transporting polypeptide-C (OATP-C, SLCO1B1), OATP-B (SLCO2B1), multidrug resistance-associated protein 2 (MRP2, ABCC2) and multidrug resistance transporter (MDR1, ABCB1) and the pharmacokinetics of pravastatin. We studied 41 healthy Caucasian volunteers who had previously participated in pharmacokinetic studies with pravastatin. Six volunteers had a very high pravastatin… 
Association of genetic polymorphism in ABCC2 with hepatic multidrug resistance-associated protein 2 expression and pravastatin pharmacokinetics
TLDR
Results support the idea that the ABCC2 c.1446C>G SNP is associated with reduced systemic exposure to pravastatin as a consequence of increased MRP2 expression, and may involve either a modulating effect of the SNP on mRNA stability or linkage to other polymorphism(s) acting at the transcriptional level.
Rapid identification of three functionally relevant polymorphisms in the OATP1B1 transporter gene using Pyrosequencing.
TLDR
The presently developed Pyrosequencing assays allowed for quick and reliable identification of those SLCO1B1 SNPs that had been proposed to cause functional alternations in OATP1 B1 with shown consequences for the pharmacokinetics of drugs that are OAT pravastatin substrates.
Influence of Drug Transporter Polymorphisms on Pravastatin Pharmacokinetics in Humans
TLDR
There is preliminary evidence to suggest that the SLCO1B1 polymorphism is not a major determinant of non-response to pravastatin, and the possible consequences of drug transporter polymorphisms for the lipid-lowering efficacy and tolerability of pravASTatin in various ethnic groups warrant further study.
Effect of drug transporter genotypes on pravastatin disposition in European- and African-American participants
TLDR
Evaluating the effects of polymorphisms in the hepatic drug uptake transporter organic anion transporting polypeptide 1B1 and efflux transporters multidrug resistance-associated protein 2, MRP2, BSEP, and BCRP on single-dose pravastatin pharmacokinetics in healthy European- and African-American participants found SLCO1B1 genotype had a significant effect on the pharmacokinetic effects.
Frequencies of single-nucleotide polymorphisms and haplotypes of the SLCO1B1 gene in selected populations of the western balkans
Abstract As a membrane influx transporter, organic anion- transporting polypeptide 1B1 (OATP1B1) regulates the cellular uptake of a number of endogenous compounds and drugs. The aim of this study was
Effects of two functionally important SLCO1B1 gene polymorphisms on pharmacokinetics of atorvastatin.
TLDR
Investigation of the effects of two functionally significant SNPs and their respective genotypes of SLCO1 B1 gene encoding OATP1B1 on the pharmacokinetics of atorvastatin found that the inter-individual variation in pharmacokinetic variation can be explained by S LCO 1B1 polymorphism.
Influence of SLCO1B1 and CYP2C8 gene polymorphisms on rosiglitazone pharmacokinetics in healthy volunteers
TLDR
It is concluded that polymorphisms in the CYP2C8 drug-metabolising enzyme gene, but not the SLCO1B1 drug transporter gene, significantly influence rosiglitazone disposition in humans.
Frequency of Single Nucleotide Polymorphisms of the SLCO1B1 Gene in Slavic Population of Central Europe
TLDR
According to the findings, analyzed SNPs in the SLCO1B1 gene are frequent enough for consideration of their screening in patients indicated for treatment with drugs involved in OATP1 B1 mediated transport.
Effects of single nucleotide polymorphisms and haplotypes of the SLCO1B1 gene on the pharmacokinetic profile of atorvastatin in healthy Macedonian volunteers.
TLDR
It is confirmed that the SLCO1B1 gene is highly polymorphic, with a frequency of the c.521T > C single-nucleotide polymorphism (SNP) being the lowest and of all other SNPs alleles above 40%, and that these SNPs may affect the inter-individual response to atorvastatin.
Frequencies of two functionally significant SNPs and their haplotypes of organic anion transporting polypeptide 1B1 SLCO1B1 gene in six ethnic groups of Pakistani population
TLDR
The 388A>G and 521T>C genotypes and corresponding haplotypes are present at varying frequencies in various ethnic groups of Pakistani population.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 52 REFERENCES
Genetic polymorphisms of human organic anion transporters OATP-C (SLC21A6) and OATP-B (SLC21A9): allele frequencies in the Japanese population and functional analysis.
TLDR
The SNP of S486F may affect the physiological function and/or pharmacological effects of OATP-B substrates in vivo, and the kinetics of uptake of [(3)H]estrone-3-sulfate was determined.
Polymorphisms in OATP-C
TLDR
The presence of multiple functionally relevant single-nucleotide polymorphisms (SNPs) in OATP-C in a population of African- and European-Americans is demonstrated and may represent a heretofore unrecognized factor influencing drug disposition.
Human Organic Anion Transporting Polypeptide-C (SLC21A6) Is a Major Determinant of Rifampin-Mediated Pregnane X Receptor Activation
TLDR
This is the first demonstration of an uptake transporter such as OATP-C, in modulating PXR function, and sheds important new insight into the understanding of the molecular determinants of P XR-mediated inductive processes.
Expression polymorphism of the blood-brain barrier component P-glycoprotein (MDR1) in relation to Parkinson's disease.
TLDR
MDR1 and other drug transporters represent plausible candidates as Parkinson's disease risk genes, and it is confirmed that the MDR1 exon 21 and exon 26 polymorphisms are in significant linkage disequilibrium.
A Naturally Occurring Mutation in the SLC21A6Gene Causing Impaired Membrane Localization of the Hepatocyte Uptake Transporter*
TLDR
Most of the mutant protein SLC21A6-L193R was retained intracellularly, and this single amino acid exchange abolished transport function, which represents the first naturally occurring mutation identified in one allele of the SLC 21A6 gene.
Polymorphisms in the ABCC2 (cMOAT/MRP2) gene found in 72 established cell lines derived from Japanese individuals: an association between single nucleotide polymorphisms in the 5'-untranslated region and exon 28.
TLDR
A strong association was found between c-24t (5'-untranslated region) and c3972t (exon 28), with the promoter activity of the former worth being compared.
Identification of functionally variant MDR1 alleles among European Americans and African Americans
TLDR
Allelic variation in MDR1 is more common than previously recognized and involves multiple SNPs whose allelic frequencies vary between populations, and some of these SNPs are associated with altered P‐glycoprotein function.
...
1
2
3
4
5
...