Abstract
The organic anion transporting polypeptide 1B1 (encoded by SLCO1B1 gene) is involved in the active cellular influx of diverse endogenous compounds and several drugs, such as HMG-CoA reductase inhibitors (statins). Two common polymorphisms c.388A>G and c.521T>C in SLCO1B1 alter transport activity of this transporter and play an important role in the pharmaceutical response to many drugs. The aim of our study was to investigate frequencies of common SNPs in SLCO1B1 gene in Western Slavic population. We determined frequencies of two common polymorphisms c.388A>G and c.521T>C in the SLCO1B1 gene in the control group consisting of 83 healthy volunteers from Slavic population by PCR-RFLP and allele-specific Real-Time PCR. Presented results were statistically evaluated and compared with known data of different ethnic groups. The allelic frequencies of SLCO1B1 SNPs were 37% for minor allele c.388G and 23% for c.521C. SLCO1B1 SNPs c.388A>G and c.521T>C were relatively frequent in Slovak population and allelic frequencies generally correspond with data published for other population of Caucasian origin. We also determined that 19% of individuals with Gilbert syndrome (ATA7/7TAA) carried the genotype c.388GG of the SLCO1B1 gene. According to our findings, analyzed SNPs in the SLCO1B1 gene are frequent enough for consideration of their screening in patients indicated for treatment with drugs involved in OATP1B1 mediated transport. Detection of polymorphisms in SLCO1B1 is beneficial for avoiding adverse drug reaction.
Highlights
Organic Anion Transporting Polypeptides (OATPs) represent family of proteins, which participate in the membrane transport of endogenous and xenobiotic compounds
83 healthy volunteers (166 alleles) from Slovak population were analyzed for 2 polymorphisms in the SLCO1B1 gene and for polymorphism A(TA)6/7TAA in the promotor region the UGT1A1 gene
Incidence of the most common SLCO1B1 SNPs is relatively common in Slovak population
Summary
Organic Anion Transporting Polypeptides (OATPs) represent family of proteins, which participate in the membrane transport of endogenous and xenobiotic compounds. The organic anion transporting polypeptide 1B1 (encoded by SLCO1B1 gene) is one of the main hepatic uptake transporters, which is localized on the basolateral part of hepatocytes. It is involved in active cellular influx of diverse endogenous substrate, such as bile acids, bilirubin, conjugates of steroid hormone and drugsHMG-CoA reductase inhibitors, fexofenadine, rifampicin, bosentan, valsartan, temocaprilat and irinotecan metabolite SN-38 (Chung et al, 2005; Pasanen et al, 2006a; Cvetkovic et al, 2009; Nishizato et al, 2003; Xiang et al, 2009; Treiber et al., 2007; Maeda et al, 2006). Interesting for genetic study are c.388A>G (rs2306283) and c. 521T>C (rs4149056) polymorphisms that resulted in the definition of SLCO1B1*B and SLCO1B1*5 respectively
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