Genetic Variations and Frequencies of the Two Functional Single Nucleotide Polymorphisms of SLCO1B1 in the Thai Population.

Chalitpon Na Nakorn,Charungthai Dejthevaporn,Jariya Waisayarat,Pornpen Srisawasdi,Sansanee Wongwaisayawan,Chonlaphat Sukasem

doi:10.3389/fphar.2020.00728

Chalitpon Na Nakorn, Charungthai Dejthevaporn + Show 4 more

Open Access

https://doi.org/10.3389/fphar.2020.00728

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Abstract

AimTo investigate the variations and the frequencies of the SLCO1B1 gene in the Thai population.MethodsCollected samples were categorized into five regions of Thailand. DNA samples were genotyped for two variants, c.388A>G and c.521T>C of the SLCO1B1, using TaqMan® real-time PCR.ResultsThe minor allele frequencies (MAFs) of two single nucleotide polymorphisms (SNPs) were not significantly different among the five regions. The most frequent haplotype was SLCO1B1*1b (frequency: 0.654), followed by *1a (frequency: 0.217), *15 (frequency: 0.128), and *5 (frequency: 0.001). We observed a similar frequency of OATP1B1 transporter phenotypes compared to other populations. 75.85% of the Thai subjects showed normal OATP1B1 activity, 22.5% showed intermediate OATP1B1 activity, and 1.58% showed low OATP1B1 activity.ConclusionThis study reported the frequencies of the SLCO1B1 variants and the subsequent OATP1B1 activity in a large cohort of Thais that can provide important information for the guidance of personalized drug therapy.

Highlights

The transmembrane protein transporters can be divided into two groups, the solute-linked carrier (SLC) superfamily or known as influx transporters, which uptake the substrate through the cells, and the ATP-binding cassette superfamily (ABC) or efflux transporters which pump the substrates out of the cells (Gong and Kim, 2013)
Genetic Variations of SLCO1B1 in Thai Population transporting polypeptides (OATPs) which are expressed in many organs such as the intestine, liver, and kidneys
OATP1B1 is a transmembrane protein expressed on the basal side of human liver cells, which regulates numerous endogenous compounds, including bilirubin, estradiol, and leukotriene C4, but it removes many drugs, such as HMG-CoA reductase inhibitors, angiotensin II receptor antagonists (ARBs), angiotensin-converting enzyme inhibitors (ACEIs), rifampicin, some antidiabetic drugs, protease inhibitors (PIs), and some chemotherapies from the blood into the hepatocytes, metabolizes and removes out of the body (Hu et al, 2012; Gong and Kim, 2013; Maeda, 2015; Alam et al, 2018)

Summary

Introduction

The transmembrane protein transporters can be divided into two groups, the solute-linked carrier (SLC) superfamily or known as influx transporters, which uptake the substrate through the cells, and the ATP-binding cassette superfamily (ABC) or efflux transporters which pump the substrates out of the cells (Gong and Kim, 2013). OATP1B1 is a transmembrane protein expressed on the basal side of human liver cells, which regulates numerous endogenous compounds, including bilirubin, estradiol, and leukotriene C4, but it removes many drugs, such as HMG-CoA reductase inhibitors (statins), angiotensin II receptor antagonists (ARBs), angiotensin-converting enzyme inhibitors (ACEIs), rifampicin, some antidiabetic drugs, protease inhibitors (PIs), and some chemotherapies from the blood into the hepatocytes, metabolizes and removes out of the body (Hu et al, 2012; Gong and Kim, 2013; Maeda, 2015; Alam et al, 2018). The polymorphisms of the SLCO1B1 gene affect the expression, localization, and function of the OATP1B1, and the drug disposition (Gong and Kim, 2013; Shitara et al, 2013)

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