Comparison of SLCO1B1 sequence variability among German, Turkish, and African populations

Mwinyi, Jessica; Köpke, Karla; Schaefer, Melanie; Roots, Ivar; Gerloff, Thomas

doi:10.1007/s00228-007-0409-y

Cited by 48 publications

(45 citation statements)

References 26 publications

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“…17) Thus, further work is required to clarify the influence of SLC22A1 polymorphisms to intracellular concentration of imatinib, because another SLC22A1 156TϾC, 480CϾG, and 1222AϾG polymorphisms may affect the intracellular concentration of imatinib. The SLCO1B1 521TϾC polymorphism, which is associated with reduced transport activity of several drugs, 35,36) could not affect the intracellular concentration of imatinib. This result is consistent with the previous report that imatinib is not transported by SLCO1B1.…”

Section: Discussionmentioning

confidence: 94%

Association of SLCO1B3 Polymorphism with Intracellular Accumulation of Imatinib in Leukocytes in Patients with Chronic Myeloid Leukemia

Nambu

Hamada

Nakashima

et al. 2011

Biological & Pharmaceutical Bulletin

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Intracellular concentration of imatinib in leukemic cells is thought to affect the clinical efficacy of this drug in patients with chronic myeloid leukemia (CML); however, there is no report that directly indicates the relationship between intracellular concentration and clinical outcome and/or, plasma concentration. In addition, the impacts of genetic variations of drug transporters, which mediate leukocyte concentration of imatinib, are unknown. In the present study, we investigated the correlation between intracellular imatinib concentrations in leukocytes, plasma imatinib levels, and genotypes of drug transporters, including ATP binding cassette B1 (ABCB), ABCG2, solute carrier 22A1 (SLC22A1), solute carrier organic anion transporter family members 1B1 (SLCO1B1) and SLCO1B3. The imatinib levels in leukocytes were determined using HPLC in 15 patients with chronic phase CML. No significant correlation between intracellular and plasma concentrations of imatinib was observed. The intracellular concentration was comparable in both patients with or without complete cytogenetic response. The intracellular imatinib concentration was significantly higher in patients with SLCO1B3 334TT than in those with 334TG/GG ( p‫؍‬ ‫.)8810.0؍‬ Plasma concentrations were similar in both SLCO1B3 genotypes (p‫؍‬ ‫,)068.0؍‬ thereby resulting in the intracellular to plasma concentration ratio being higher in patients with SLCO1B3 334TT than those with 334 TG/GG ( p‫؍‬ ‫.)2050.0؍‬ These results suggested that the SLCO1B3 334TϾ ϾG polymorphism could have a significant impact on the intracellular concentration of imatinib in leukocytes as a promising biomarker for personalized treatment of CML patients.

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Section: Discussionmentioning

confidence: 94%

Association of SLCO1B3 Polymorphism with Intracellular Accumulation of Imatinib in Leukocytes in Patients with Chronic Myeloid Leukemia

Nambu

Hamada

Nakashima

et al. 2011

Biological & Pharmaceutical Bulletin

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“…In vitro assays have consistently validated altered transport efficiency in at least 13 [45], only 1% of Japanese subjects carry this allele [46]. For this reason, studies evaluating associations between SLCO1B1*5 and clinical outcome in Caucasians have been more statistically powered and have resulted in clearer clinical outcomes [45,47,48]. The SLCO1B3 gene has four polymorphisms (…”

Section: Genetic Variation and Genotyping Methodsmentioning

confidence: 99%

Pharmacogenetics of Membrane Transporters: An Update on Current Approaches

et al. 2009

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This review provides an overview of the pharmacogenetics of membrane transporters including selected ABC transporters (ABCB1, ABCC1, ABCC2, and ABCG2) and OATPs (OATP1B1 and OATP1B3). Membrane transporters are heavily involved in drug clearance and alters drug disposition by actively transporting substrate drugs between organs and tissues. As such, polymorphisms in the genes encoding these proteins may have significant effects on the absorption, distribution, metabolism and excretion of compounds, and may alter pharmacodynamics of many agents. This review discusses the techniques used to identify substrates and inhibitors of these proteins and subsequently to assess the effect of genetic mutation on transport, both in vitro and in vivo. A comprehensive list of substrates for the major drug transporters is included. Finally, studies linking transporter genotype with clinical outcomes are discussed.

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“…Considering the highly frequent occurrence of the variant SLCO1B1 c.521C allele in the European population [9][10][11][12], the implementation of SLCO1B1 c.521T>C genotyping has clinical relevance, especially in individuals treated with statins. Both real-time PCR assays evaluated here demonstrated a concordance of 100% (κ = 1, p < 0.001) for all genotype groups thereby providing an important quality attribute for patient safety in genetic testing.…”

Section: Discussionmentioning

confidence: 99%

“…To identify individuals at significant risk, the clinical implementation of SL-CO1B1 c.521T>C testing is recommended [7,8]. It is well known that the SLCO1B1 c.521C allele occurs more frequently in Europeans (10-20%), Asians (10-15%), and Americans (20%) than in Africans (2-4%) [9,10]. However, detailed data about the frequency distribution in the Austrian population is still lacking.…”

Section: Introductionmentioning

confidence: 99%

<b><i>SLCO1B1</i></b> c.521T>C Genotyping in the Austrian Population Using 2 Commercial Real-Time Polymerase Chain Reaction Assays: An Implementation Study

Enko

Harringer

Oberkanins³

et al. 2018

Pharmacology

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Statin-induced myopathy is reported to be significantly associated with the SCLO1B1 c.521T>C polymorphism. To date, SLCO1B1 c.521T>C epidemiologic data for the Austrian population is still lacking. Therefore, this study aimed at assessing the genotype and allele frequencies of the SLCO1B1 c.521T>C variant in Austria and evaluating the clinical performance of 2 commercial real-time polymerase chain reaction (PCR) assays. Genomic DNA isolated from 181 healthy individuals was analyzed for the SLCO1B1 c.521T>C polymorphism in a comparative manner using the SLCO1B1 c.521T>C RealFast^TM Assay and the BioPro SLCO1B1 Genotyping real-time PCR Kit. A total of 10 (5.5%) and 44 (24.3%) out of 181 individuals were SLCO1B1 c.521T>C C/C-homo- and C/T-heterozygotes, the genotypes indicative of high and increased risk of statin-induced myopathy, respectively. The SLCO1B1 c.521C allele frequency rate was 17.7%. In conclusion, the genetic predisposition of elevated statin-induced myopathy risk in the Austrian population is frequent. Both real-time PCR assays under investigation here are reliable and robust SLCO1B1 c.521T>C genotyping tools in clinical routine.

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Comparison of SLCO1B1 sequence variability among German, Turkish, and African populations

Abstract: 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.

Cited by 48 publications

References 26 publications

Association of SLCO1B3 Polymorphism with Intracellular Accumulation of Imatinib in Leukocytes in Patients with Chronic Myeloid Leukemia

Association of SLCO1B3 Polymorphism with Intracellular Accumulation of Imatinib in Leukocytes in Patients with Chronic Myeloid Leukemia

Pharmacogenetics of Membrane Transporters: An Update on Current Approaches

<b><i>SLCO1B1</i></b> c.521T>C Genotyping in the Austrian Population Using 2 Commercial Real-Time Polymerase Chain Reaction Assays: An Implementation Study

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Comparison of SLCO1B1 sequence variability among German, Turkish, and African populations

Abstract: 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.

Cited by 48 publications

References 26 publications

Association of SLCO1B3 Polymorphism with Intracellular Accumulation of Imatinib in Leukocytes in Patients with Chronic Myeloid Leukemia

Association of SLCO1B3 Polymorphism with Intracellular Accumulation of Imatinib in Leukocytes in Patients with Chronic Myeloid Leukemia

Pharmacogenetics of Membrane Transporters: An Update on Current Approaches

<b><i>SLCO1B1</i></b> c.521T&gt;C Genotyping in the Austrian Population Using 2 Commercial Real-Time Polymerase Chain Reaction Assays: An Implementation Study

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Product

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<b><i>SLCO1B1</i></b> c.521T>C Genotyping in the Austrian Population Using 2 Commercial Real-Time Polymerase Chain Reaction Assays: An Implementation Study