SLCO1B1 and ABCG2 Gene Polymorphisms in a Thai Population

Punyabhorn Rattanacheeworn; Monpat Chamnanphon; Siriwan Thongthip; Wonngarm Kittanamongkolchai; Natavudh Townamchai; Yingyos Avihingsanon; Udomsak Udomnilobol; Thomayant Prueksaritanont; Suree Jianmongkol; Pajaree Chariyavilaskul

doi:10.2147/PGPM.S268457

SLCO1B1 and ABCG2 Gene Polymorphisms in a Thai Population

Pharmgenomics Pers Med. 2020 Oct 22:13:521-530. doi: 10.2147/PGPM.S268457. eCollection 2020.

Authors

Affiliations

¹ Clinical Pharmacokinetics and Pharmacogenomics Research Unit, Chulalongkorn University, Bangkok, Thailand.
² Department of Pharmacology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
³ Maha Chakri Sirindhorn Clinical Research Center Under the Royal Patronage, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
⁴ Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
⁵ Chulalongkorn University Drug and Health Products Innovation Promotion Center, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.
⁶ Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.

Abstract

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: ABCG2; BRCP; OATP1B1; SLCO1B1; drug transporters; pharmacogenetics; pharmacogenomics.

Grants and funding

This work was supported by the Health Systems Research Institute (HSRI) grant no. 60094. Rattanacheeworn, P. was supported by the 100th Anniversary Chulalongkorn University Fund for Doctoral Scholarship. We thank the staff of the HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT) laboratory for their technical assistance.