SLCO1B1 and ABCG2 Gene Polymorphisms in a Thai Population
Received 19 June 2020
Accepted for publication 21 September 2020
Published 22 October 2020 Volume 2020:13 Pages 521—530
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Martin Bluth
Punyabhorn Rattanacheeworn,1,2 Monpat Chamnanphon,1 Siriwan Thongthip,3 Wonngarm Kittanamongkolchai,3 Natavudh Townamchai,1,4 Yingyos Avihingsanon,1,4 Udomsak Udomnilobol,5 Thomayant Prueksaritanont,5 Suree Jianmongkol,5,6 Pajaree Chariyavilaskul1,2
1Clinical Pharmacokinetics and Pharmacogenomics Research Unit, Chulalongkorn University, Bangkok, Thailand; 2Department of Pharmacology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; 3Maha Chakri Sirindhorn Clinical Research Center Under the Royal Patronage, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; 4Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; 5Chulalongkorn University Drug and Health Products Innovation Promotion Center, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand; 6Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand
Correspondence: Pajaree Chariyavilaskul
Department of Pharmacology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
Fax +6622564481 Ext.1
Introduction: Genetic polymorphisms of drug transporters influence drug transporter activity and alter pharmacokinetic profiles of the drugs. Organic anion transporting polypeptide 1B1 (OATP1B1) and breast cancer resistance protein (BCRP) are important transporters encoded by solute carrier organic anion transporter family member 1B1 (SLCO1B1) gene and ATP-binding cassette subfamily G member 2 (ABCG2) gene, respectively. Polymorphisms in these genes are associated with increased plasma statins concentrations, statin-induced myopathy and poor response to allopurinol treatment.
Purpose: We explored allele and genotype frequencies of SLCO1B1 and ABCG2 genes including their predicted phenotypes in 53 Thai participants. Of these, 17 had chronic kidney disease and were on statins.
Materials and Methods: Genotyping analysis for SLCO1B1 c.521T>C (rs4149056), c.388A>G (rs2306283), g.-11187G>A (rs4149015), and ABCG2 c.421C>A (rs2231142) was done by using TaqMan® Real time PCR. All were tested for Hardy–Weinberg Equilibrium.
Results: Most of the participants (80%) had normal function haplotypes SLCO1B1 (*1A and *1B) while decreased (*5, *15, and *17) and unknown (*21) function haplotypes were less observed. Four phenotypes of SLCO1B1 were observed: 69.81% had normal function (*1A/*1A,*1A/*1B, and *1B/*1B), 13.21% had intermediate function (*1A/*17, *1B/*15 and *1B/*17), 9.43% had indeterminate function (*1A/*21 and *1B/*21) and 7.55% had low function (*5/*15, *15/*15, and *15/*17). ABCG2 c.421A allele frequency was 25%. The frequency of ABCG2 c.421CA and AA phenotypes were 37.7% and 5.7%, respectively. The allele and genotype frequencies observed are consistent with reports in Asians. However, there were differences in major allele distributions between Asians and Caucasians for SLCO1B1 c.388A>G; SLCO1B1 c.388G were highly found in Asians, but c.388A were more observed in Caucasians.
Conclusion: This study showed that in the Thai population, there were 4 SNPs of SLCO1B1 and ABCG2 genes. This finding may be clinically applied to minimize inter-individual variability of drugs such as statins and allopurinol. Further study with a larger sample size is needed to assess the drug profiles and responses to treatment.
Keywords: pharmacogenetics, pharmacogenomics, drug transporters, SLCO1B1, ABCG2, OATP1B1, BRCP
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