Comparison of SLCO1B1 sequence variability among German, Turkish, and African populations
Autor: | Karla Köpke, Ivar Roots, Melanie Schaefer, Thomas Gerloff, Jessica Mwinyi |
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Rok vydání: | 2008 |
Předmět: |
Male
Turkey Black People Organic Anion Transporters Biology Polymerase Chain Reaction Polymorphism Single Nucleotide White People chemistry.chemical_compound Gene Frequency Pharmacokinetics Polymorphism (computer science) Germany Genotype Humans Pharmacology (medical) Genetic variability Gene Alleles Pharmacology Genetics Base Sequence Liver-Specific Organic Anion Transporter 1 Sequence Analysis DNA General Medicine Haplotypes chemistry Africa biology.protein Female SLCO1B1 Xenobiotic Polymorphism Restriction Fragment Length Function (biology) |
Zdroj: | European Journal of Clinical Pharmacology. 64:257-266 |
ISSN: | 1432-1041 0031-6970 |
DOI: | 10.1007/s00228-007-0409-y |
Popis: | OATP1B1 is one of the key hepatocellular uptake transporters providing extraction of diverse compounds, including bile acids, xenobiotics, and a variety of drugs, from portal venous blood into the liver. Polymorphisms of the SLCO1B1 gene have been demonstrated to influence in vitro transport function and the pharmacokinetic profile of compounds.The goal of our study was the comparison of SLCO1B1 gene sequence variability in three ethnic groups as a basis for future genetic association studies.Eighteen exonic SLCO1B1 single nucleotide polymorphisms (SNPs) were genotyped by PCR and RFLP analysis in 300 German, 94 Turkish, and 115 African subjects. Calculation of pairwise linkage disequilibrium and estimation of population haplotype frequencies were carried out, and haplotype block structure was determined.Only eight genotyped SNPs (c.388AG, c.411GA, c.463CA, c.521TC, c.571CT, c.597CT, c.1463GC, c.1929AC) were found in at least one of our German, Turkish, or African samples. A total of 12 haplotypes with a frequencyor=1% in at least one of the three populations could be inferred. Between the Caucasian and African samples, significant differences in sequence variability were observed leading to a different haplotype profile in these populations.Our results demonstrate a high sequence variability of OATP1B1 within different popuations. In the future, distinct haplotypes should be taken into account when studying the effect of OATP1B1 on drugs in different populations. |
Databáze: | OpenAIRE |
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