Comparison of genetic variations of the SLCO1B1, SLCO1B3, and SLCO2B1 genes among five ethnic groups

Namgoong, Suhg; Cheong, Hyun Sub; Kim, Ji On; Kim, Lyoung Hyo; Na, Han Sung; Koh, In Song; Chung, Myeon Woo; Shin, Hyoung Doo

doi:10.1016/j.etap.2015.08.033

Cited by 10 publications

(8 citation statements)

References 28 publications

(35 reference statements)

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“…This study provides an insight into the general pharmaco kinetic mechanisms behind simvastatin-induced myopathy related to various factors. The frequencies of the SLCO1B1 c.521C allele (13.0%) and the ABCB1 c.1236T-2677T-3435T haplo type (33%) observed in our study were similar to those previously reported [22,23]. Despite the sample sizes being unbalanced between the two genes (i.e., the number of SLCO1B1 T/T vs T/C = 16:10; ABCB1 CGC/CGC vs TTT/TTT = 13:13), their effects can be measured and compared using a linear-mixed model [24].…”

Section: Discussionsupporting

confidence: 92%

The Influences of SLCO1B1 and ABCB1 Genotypes on the Pharmacokinetics of Simvastatin, in Relation to CYP3A4 Inhibition

et al. 2017

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Aim:To investigate the combined effects of SLCO1B1 and ABCB1 genotypes on the pharmacokinetics of simvastatin and its active metabolite simvastatin acid, in relation to CYP3A4 inhibition. Methods: We conducted a single-dose pharmacokinetic study of simvastatin in 26 healthy volunteers screened for their SLCO1B1 c.521T>C and ABCB1 c.1236C>T-2677G>T-3435C>T genotypes, with and without amlodipine pretreatment. The genetic effects and drug-interaction effect on simvastatin pharmacokinetic parameters were analyzed using a linear-mixed model. Results: The SLCO1B1 c.521T>C variant significantly increased exposure to simvastatin acid by around 40% (p < 0.05), similar to that caused by the amlodipine pretreatment. The ABCB1 gene showed no influence on exposure to simvastatin or simvastatin acid. Conclusion: Only SLCO1B1, not ABCB1 genotype, is likely to be associated with simvastatin-induced myopathy. SLCO1B1 genotyping may be particularly beneficial in simvastatin users who are co-administered CYP3A4 inhibitors.

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Section: Discussionsupporting

confidence: 92%

The Influences of SLCO1B1 and ABCB1 Genotypes on the Pharmacokinetics of Simvastatin, in Relation to CYP3A4 Inhibition

et al. 2017

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“…63 The focus of this section will be on OATP1B1 and OATP1B3, as these have been shown to be important hepatic uptake transporters with involvement in drug-drug interactions and alterations in drug response. SLCO1B1 388A>G increases hepatic uptake activity and is present in 40% of whites, 75% of African Americans, and 60% of Asians, [64][65][66][67] whereas SLCO1B1 521T>C decreases hepatic uptake activity and has a S87 lower prevalence across ethnic groups (15% of whites, 2% of African Americans, and 15% of Asians). [64][65][66][67] Two haplotypes that decrease uptake activity leading to increased substrate exposure are SLCO1B1*5 (c.388Ac.521C) and SLCO1B1*15 (c.388G-c.521C).…”

Section: Bcrp Inhibitorsmentioning

confidence: 99%

“…SLCO1B1 388A>G increases hepatic uptake activity and is present in 40% of whites, 75% of African Americans, and 60% of Asians, whereas SLCO1B1 521T>C decreases hepatic uptake activity and has a lower prevalence across ethnic groups (15% of whites, 2% of African Americans, and 15% of Asians) . Two haplotypes that decrease uptake activity leading to increased substrate exposure are SLCO1B1*5 (c.388A‐c.521C) and SLCO1B1*15 (c.388G‐c.521C) …”

Section: Evaluation Of Proposed In Vivo Transporter Probesmentioning

confidence: 99%

Evaluation of Proposed In Vivo Probe Substrates and Inhibitors for Phenotyping Transporter Activity in Humans

Momper

Tsunoda

Joseph

2016

The Journal of Clinical Pharma

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Drug transporters are present in various tissues and have a significant role in drug absorption, distribution, and elimination. The International Transporter Consortium has identified 7 transporters of increasing importance from evidence of clinically significant transporter-mediated drug-drug interactions. The transporters are P-glycoprotein, breast cancer resistance protein, organic anion transporting polypeptide (OATP) 1B1, OATP1B3, organic cation transporter 2, organic anion transporters (OAT) 1, and OAT3. Decision trees were created based on in vitro experiments to determine whether an in vivo transporter-mediated drug-drug interaction study is needed. Phenotyping is a methodology that evaluates real-time in vivo transporter activity, whereby changes in a probe substrate or probe inhibitor reflect alternations in the activity of the specified transporter. In vivo probe substrates and/or probe inhibitors have been proposed for each aforementioned transporter. In vitro findings and animal models provide the strongest evidence regarding probe specificity. However, such findings have not conclusively correlated with human phenotyping studies. Furthermore, the extent of contribution from multiple transporters in probe disposition complicates the ability to discern if study findings are the result of a specific transporter and thus provide a recommendation for a preferred probe for a drug transporter.

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“…The SLCO2B1 gene encoding OATP2B1 harbors polymorphic variations whose frequencies vary among different ethnic groups (139). Nonsynonymous genetic variations of OATP2B1 (c.935G>A and c.1457C>T; dbSNP-IDs of rs12422149 and rs230618) have been associated with the altered transport activity and PK changes in vivo, with some conflicting results (140)(141)(142)(143).…”

Section: Oatp2b1mentioning

confidence: 99%

Post-translational regulation of the major drug transporters in the families of organic anion transporters and organic anion–transporting polypeptides

Lee

Sugiyama

2020

Journal of Biological Chemistry

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The Organic Anion Transporters (OATs) and Organic Anion Transporting Polypeptides (OATPs) belong to the solute carrier (SLC) transporter superfamily and play important roles in handling various endogenous and exogenous compounds of anionic charge. The OATs and OATPs are often implicated in drug therapy by impacting the pharmacokinetics of clinically important drugs and thereby, drug exposure in the target organs or cells. Various mechanisms (e.g., genetic, environmental, and disease-related factors, drug-drug interactions, and food-drug interactions) can lead to variations in the expression and activity of the anion drug-transporting proteins of OATs and OATPs, possibly impacting the therapeutic outcomes. Previous investigations mainly focused on the regulation at the transcriptional level and drug-drug interactions as competing substrates or inhibitors. Recently evidence has accumulated that cellular trafficking, post-translational modification, and degradation mechanisms serve as another important layer for the mechanisms underlying the variations in the OATs and OATPs. This review will provide a brief overview of the major OATs and OATPs implicated in drug therapy and summarize recent progress in our understanding of the post-translational modifications, in particular, ubiquitination and degradation pathways of the individual OATs and OATPs implicated in drug therapy.

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Comparison of genetic variations of the SLCO1B1, SLCO1B3, and SLCO2B1 genes among five ethnic groups

Cited by 10 publications

References 28 publications

The Influences of SLCO1B1 and ABCB1 Genotypes on the Pharmacokinetics of Simvastatin, in Relation to CYP3A4 Inhibition

The Influences of SLCO1B1 and ABCB1 Genotypes on the Pharmacokinetics of Simvastatin, in Relation to CYP3A4 Inhibition

Evaluation of Proposed In Vivo Probe Substrates and Inhibitors for Phenotyping Transporter Activity in Humans

Post-translational regulation of the major drug transporters in the families of organic anion transporters and organic anion–transporting polypeptides

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