Drug Transporters Polymorphism Among Indonesian Population: A Review
DOI:
https://doi.org/10.57125/FEM.2025.06.30.04Keywords:
pharmacogenetics, drug transporters, polymorphisms, personalized medicineAbstract
Genetic polymorphisms in drug transporters markedly affect drug absorption, distribution, and elimination, thereby contributing to interindividual variability in pharmacological responses. A comprehensive understanding of these genetic variations is essential for the advancement of personalized medicine, especially within genetically heterogeneous populations such as Indonesia.
Aims: This investigation seeks to elucidate the influence of drug transporter polymorphisms on therapeutic outcomes and their ramifications for personalized medicine in the Indonesian context. This study amalgamates existing research to furnish insights into genetic variations that impact drug metabolism, aiding the optimization of pharmacotherapy practices in Indonesia.
Methodology: A systematic literature review was performed utilizing the PubMed database, identifying studies published between 2013 and 2025 that pertain to drug transporter polymorphisms within the Indonesian cohort. The data extraction process concentrated on the pharmacokinetic and pharmacodynamic implications of genetic variations in pivotal transporters.
Results: A total of twelve studies were analyzed, predominantly focusing on SLC22A1, SLCO1B1, and ABCB1 polymorphisms in connection with the treatment of diabetes, cancer, epilepsy, hypercholesterolemia, and tuberculosis. The SLC22A1 Met420del variant was associated with modified metformin pharmacokinetics, while SLCO1B1 polymorphisms influenced statin metabolism, and ABCB1 variants were investigated concerning chemotherapy drug resistance. Nevertheless, inconsistent clinical significance was noted, attributable to limited sample sizes and discrepancies in methodologies.
Scientific Novelty: This study underscores the imperative to incorporate pharmacogenetic principles into Indonesia's healthcare framework while addressing challenges such as research funding, restricted access to diverse samples, and lack of pharmacogenetic knowledge among practitioners. This research uniquely consolidates evidence regarding genetic determinants that influence drug metabolism in Indonesia, thereby establishing a foundational basis for personalized medicine initiatives within a genetically diverse population.
Conclusion: Pharmacogenetics can optimize resources, decrease side effects, and increase treatment efficacy. Future initiatives should prioritize expanded research, public awareness, and governmental support to ensure the effective implementation of personalized medicine in Indonesia.
References
Simanjuntak R, Sutrisman H, Prihartanto A, Ramadhona R. Pharmacogenomic analysis in determining optimal drug dosage in chronic disease patients in Indonesia. Int J Public Health. 2024;1(3). https://doi.org/10.62951/ijph.v1i3.74
Cavallari LH, Hicks JK, Patel JN, Elchynski AL, Smith DM, Bargal SA, et al. The Pharmacogenomics Global Research Network Implementation Working Group: global collaboration to advance pharmacogenetic implementation. Pharmacogenet Genomics. 2024. https://doi.org/10.1097/fpc.0000000000000547
Koo SH, Lo YL, Yee JY, Lee EJD. Genetic and/or non-genetic causes for inter-individual and inter-cellular variability in transporter protein expression: implications for understanding drug efficacy and toxicity. Expert Opin Drug Metab Toxicol. 2015;11(12):1933–45. https://doi.org/10.1517/17425255.2015.1104298
Chan SL, Jin S, Loh M, Brunham LR. Progress in understanding the genomic basis for adverse drug reactions: a comprehensive review and focus on the role of ethnicity. Pharmacogenomics. 2015;16(16):1905–26. https://doi.org/10.2217/pgs.15.54
Bachtiar M, Ooi BNS, Wang J, Jin Y, Tan TW, Chong SS, et al. Towards precision medicine: interrogating the human genome to identify drug pathways associated with potentially functional, population-differentiated polymorphisms. Pharmacogenomics J. 2019;19(5):419–28. https://doi.org/10.1038/s41397-019-0096-y
Atmaja SP, Rawar E, Kristiyani A, Nugrahaningsih DAA, Sadewa AH, Patramurti C. The genetic polymorphisms of CYP3A41G and CYP3A53 in Javanese Indonesian population. J Trop Life Sci. 2024;14(1):51–6. https://doi.org/10.11594/jtls.14.01.06
Santoso P, Juliastuti H, Nataprawira HM, Soeroto AY, Alisjahbana B, Ruslami R, Debora J, Sribudiani Y, Maskoen AM. Polymorphisms of SLCO1B1 Gene in Sundanese Ethnic Population of Tuberculosis Patients in Indonesia. Acta Med Indones. 2022 Oct;54(4):517-523. PMID: 36624704.
Hidayat R, Rasyid A, Harris S, Harahap A, Herqutanto H, Louisa M, et al. Impact of Cyp2c19 Allele 17 Mutase on Clopidogrel Hyper-Responsiveness in Indonesian Patients with Ischemic Stroke. Open Access Maced J Med Sci. 2023;11(G):367–74. https://doi.org/10.3889/oamjms.2023.11558
Alvina AP, Zullies I, Sri S, Anindya R. High Frequency of the Opioid Receptor µ-1 (OPRM1) A118G Polymorphism, an Opioid Drug Therapy Related Gene, in the Indonesian Population. Curr Pharmacogenomics Pers Med. 2020;18(3):213–9. https://doi.org/10.2174/1875692117666191211154755
Banerjee BD, Kumar R, Thamineni KL, Shah HK, Thakur GK, Sharma T. Effect of environmental exposure and pharmacogenomics on drug metabolism. Curr Drug Metab. 2020;21(1):3–11. https://doi.org/10.2174/1389200221666200110153304
Jamshidi N, Nigam SK. Drug transporters OAT1 and OAT3 have specific effects on multiple organs and gut microbiome as revealed by contextualized metabolic network reconstructions. Sci Rep. 2022;12:18242. https://doi.org/10.1038/s41598-022-21091-w
Liang X, Staiger KM, Riddle E, Hao J, Lai Y. Role of transporters in drug disposition and drug-drug interactions. In: Varma MV, El-Kattan A, editors. ADME-enabling technologies in drug design and development. 1st ed. San Diego (CA): Academic Press; 2020. p. 275–300. DOI: https://doi.org/10.1016/B978-0-12-820018-6.00010-7
Kothary AS, Mahendra C, Tan M, Tan EJM, Yi JPH, Gabriella G, et al. Validation of a multi-gene qPCR-based pharmacogenomics panel across major ethnic groups in Singapore and Indonesia. Pharmacogenomics. 2021;22(14):857–69. https://doi.org/10.2217/pgs-2021-0071
Tremmel R, Zhou Y, Camara MD, Laarif S, Eliasson E, Lauschke VM. PharmFreq: a comprehensive atlas of ethnogeographic allelic variation in clinically important pharmacogenes. Nucleic Acids Res. 2024;52(D1):D1181–9. https://doi.org/10.1093/nar/gkae1016
Ausi Y, Barliana MI, Postma MJ, Suwantika AA. One Step Ahead in Realizing Pharmacogenetics in Low- and Middle-Income Countries: What Should We Do? J Multidiscip Healthc. 2024;17:101–8. https://doi.org/10.2147/JMDH.S458564
Dizon JM, Machingaidze S, Grimmer K. To adopt, to adapt, or to contextualise? The big question in clinical practice guideline development. BMC Res Notes. 2016;9:442. https://doi.org/10.1186/s13104-016-2244-7
Widyahening IS, Wangge G, van der Graaf Y, van der Heijden GJMG. Adapting clinical guidelines in low-resources countries: a study on the guideline on the management and prevention of type 2 diabetes mellitus in Indonesia. J Eval Clin Pract. 2017;23(1):121–7. https://doi.org/10.1111/jep.12628
Perwitasari DA, Wessels JAM, van der Straaten RJHM, Baak-Pablo R, Mustofa M, Nortier JWR, et al. Association of ABCB1, 5-HT3B receptor and CYP2D6 genetic polymorphisms with ondansetron and metoclopramide antiemetic response in Indonesian cancer patients treated with highly emetogenic chemotherapy. Jpn J Clin Oncol. 2011;41(11):1302–9. https://doi.org/10.1093/jjco/hyr117
Kulma I, Boonprasert K, Na-Bangchang K. Polymorphisms of genes encoding drug transporters or cytochrome P450 enzymes and association with clinical response in cancer patients: a systematic review. Cancer Chemother Pharmacol. 2019;84(3):405–22. https://doi.org/10.1007/s00280-019-03932-0
Pasternak AL, Ward KM, Irwin M, Okerberg C, Hayes D, Fritsche LG, et al. Identifying the prevalence of clinically actionable drug‐gene interactions in a health system biorepository to guide pharmacogenetics implementation services. Clin Transl Sci. 2022;15(5):1217–25. https://doi.org/10.1111/cts.13449
Maharani L, Yugatama A. Prevalence of adverse drug reaction in Indonesia: A systematic review. J Appl Pharm Sci [Internet]. 2023; Available from: http://dx.doi.org/10.7324/japs.2023.91550
Hasni D, Siregar KB, Lim H. The influence of glutathion S-transferase P-1 polymorphism A313G rs1695 on the susceptibility to cyclophosphamide hematologic toxicity in Indonesian patients. Medical Journal of Indonesia. 2016 Jul 26;25(2):118–26. https://doi.org/10.13181/mji.v25i2.1308
Rinaldi I, Nova R, Widyastuti R, Priambodo R, Instiaty I, Louisa M. Association between C1236T genetic variant of ABCB1 gene and molecular response to imatinib in Indonesian chronic myeloid patients. Asian Pac J Cancer Prev. 2019;20(11):3331–4. https://doi.org/10.31557/APJCP.2019.20.11.3331
Syarifah S, Widyawati T, Hasni D, Sari MI, Rusdiana R, Hamdi T. The Relation of Haplotype ATP-binding Cassette B1 and Glutathione S-transferase P1 A313G Genes with Hematological Toxicity in Indonesian Breast Cancer Patients Receiving Chemotherapy. Oman Med J. 2022 Mar 22;37(2):e357. doi: 10.5001/omj.2022.36. PMID: 35402005; PMCID: PMC8976885.
Perwitasari DA, Attobari J. Polymorphism of organic cation transporter 1 (OCT1) in Indonesian cancer patients. Int J Pharm Pharm Sci. 2014;6(5):380–2.
Barliana MI, Kusuma ASW, Insani WN, Alfian SD, Diantini A, Mutakin M, et al. Genetic variation of ABCB1 (rs1128503, rs1045642) and CYP2E1 rs3813867 with the duration of tuberculosis therapy: a pilot study among tuberculosis patients in Indonesia. BMC Res Notes. 2021;14(1). https://doi.org/10.1186/s13104-021-05711-8
Ang SA, Nugroho AK, Sadewa AH, Hakim L, Mustofa. The SLCO1B1*15 haplotype associated with lower clinical outcome in Indonesian tuberculosis patients. Berkala Ilmu Kedokteran [Internet]. 2018;50(01):50–9. Available from: http://dx.doi.org/10.19106/jmedsci005001201806
Ningrum VD, Istikharah R, Firmansyah R. Allele frequency of SLC22A1 Met420del metformin main transporter encoding gene among Javanese-Indonesian population. Open Access Maced J Med Sci. 2019 Feb 14;7(3):378–83. doi:10.3889/oamjms.2019.087. PMID: 30834005; PMCID: PMC6390162.
Ningrum VDA, Ikawati Z, Sadewa AH, Ikhsan MR. Allele frequencies of two main metformin transporter genes: SLC22A1 rs628031 A>G and SLC47A1 rs2289669 G>A among the Javanese population in Indonesia. Curr Pharmacogenomics Person Med. 2018 Feb 21;15(2):121–8.
Aryastuti SA, Sintya E, Asri Lestarini AL, Witari NPD. Allele frequency of a common variant and two common loss-of-function variants in organic cation transporter 1 (OCT1) among Balinese diabetic patients. Biomed Pharmacol J. 2022 Mar 31;15(1):269–75. doi:10.13005/bpj/2363.
Istikharah R, Hartienah SD, Vitriyani S, Ningrum VDA. Allele frequency of carbamazepine major efflux transporter encoding gene ABCB1 C3435T among Javanese-Indonesian population. Open Access Maced J Med Sci. 2020 Jul 20;8(A):406–13. doi:10.3889/oamjms.2020.4184.
Budikayanti A, Khosama H, Octaviana F, Hamid DH, Louisa M, Ranakusuma TAS, Setiabudy R. Multidrug resistance-1 C3435T polymorphism and carbamazepine plasma level in Indonesian temporal lobe epilepsy patients. Curr Drug Saf. 2023;18(1):62–8. doi:10.2174/1574886317666220414130526. PMID: 35430998.
Andrianto, Puspitasari M, Ardiana M, Dewi IP, Shonafi KA, Kusuma Wardhani LF, Nugraha RA. Association between single nucleotide polymorphism SLCO1B1 gene and simvastatin pleiotropic effects measured through flow-mediated dilation endothelial function parameters. Ther Adv Cardiovasc Dis. 2022;16:17539447221132367. doi:10.1177/17539447221132367. PMID: 36314075.
Hidayat R, Nabilah RA, Fisher M, Aninditha T, Kurniawan M, Estiasari R, et al. The association between ABCB1 gene polymorphism and clopidogrel response variability in ischemic stroke: a cross-sectional study. BMC Neurol. 2024 Jun 24;24(1):216. doi:10.1186/s12883-024-03723-y. PMID: 38914966; PMCID: PMC11194867.
Chasman DI, Giulianini F, MacFadyen J, Barratt BJ, Nyberg F, Ridker PM. Genetic determinants of statin-induced low-density lipoprotein cholesterol reduction. Circ Cardiovasc Genet. 2012 Apr;5(2):257–64. doi:10.1161/CIRCGENETICS.111.961144.
Bailey KM, Romaine SPR, Jackson BM, Farrin AJ, Efthymiou M, Barth JH, et al. Hepatic metabolism and transporter gene variants enhance response to rosuvastatin in patients with acute myocardial infarction. Circ Cardiovasc Genet. 2010 Jun;3(3):276–85. doi:10.1161/CIRCGENETICS.109.898502.
Chu AY, Giulianini F, Grallert H, Dupuis J, Ballantyne CM, Barratt BJ, et al. Genome-wide association study evaluating lipoprotein-associated phospholipase A2 mass and activity at baseline and after rosuvastatin therapy. Circ Cardiovasc Genet. 2012 Dec;5(6):676–85. doi:10.1161/CIRCGENETICS.112.963314.
SEARCH Collaborative Group, Link E, Parish S, Armitage J, Bowman L, Heath S, et al. SLCO1B1 variants and statin-induced myopathy: a genomewide study. N Engl J Med. 2008 Aug 21;359(8):789–99. doi:10.1056/NEJMoa0801936. PMID: 18650507.
Voora D, Shah SH, Spasojevic I, Ali S, Reed CR, Salisbury BA, Ginsburg GS. The SLCO1B1*5 genetic variant is associated with statin-induced side effects. J Am Coll Cardiol. 2009 Oct 20;54(17):1609–16. doi: 10.1016/j.jacc.2009.04.053. PMID: 19833260; PMCID: PMC3417133.
Postmus I, Trompet S, Deshmukh HA, Barnes MR, Li X, Warren HR, et al. Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins. Nat Commun. 2014 Oct 28;5:5068. doi: 10.1038/ncomms6068.
Akao H, Polisecki E, Kajinami K, Trompet S, Robertson M, Ford I, et al. Genetic variation at the SLCO1B1 gene locus and low density lipoprotein cholesterol lowering response to pravastatin in the elderly. Atherosclerosis. 2012 Feb;220(2):413–7. doi: 10.1016/j.atherosclerosis.2011.09.028.
Shu Y, Brown C, Castro R, Shi R, Lin E, Owen R, et al. Effect of genetic variation in the organic cation transporter 1, OCT1, on metformin pharmacokinetics. Clin Pharmacol Ther. 2008 Feb;83(2):273–80. doi: 10.1172/JCI30558.
Sundelin E, Gormsen L, Jensen J, Vendelbo M, Jakobsen S, Munk O, et al. Genetic polymorphisms in organic cation transporter 1 attenuate hepatic metformin exposure in humans. Clin Pharmacol Ther. 2017 Nov;102(5):841–8. doi: 10.1002/cpt.701.
Tzvetkov MV, Saadatmand AR, Bokelmann K, Meineke I, Kaiser R, Brockmöller J. Effects of OCT1 polymorphisms on the cellular uptake, plasma concentrations and efficacy of the 5-HT3 antagonists tropisetron and ondansetron. Pharmacogenomics J. 2012 Feb;12(1):22–9. doi: 10.1038/tpj.2010.75.
Christensen MMH, Højlund K, Hother-Nielsen O, Stage TB, Damkier P, Beck-Nielsen H, et al. Endogenous glucose production increases in response to metformin treatment in the glycogen-depleted state in humans: a randomised trial. Diabetologia. 2015 Nov;58(11):2494–502. doi: 10.1007/s00125-015-3733-2.
Dujic T, Zhou K, Yee S, van Leeuwen N, de Keyser C, Javorský M, et al. Variants in pharmacokinetic transporters and glycemic response to metformin: a MetGen meta-analysis. Clin Pharmacol Ther. 2017 Jun;101(6):763–72. doi: 10.1002/cpt.567.
Jablonski KA, McAteer JB, de Bakker PIW, Franks PW, Pollin TI, Hanson RL, et al. Common variants in 40 genes assessed for diabetes incidence and response to metformin and lifestyle intervention in the Diabetes Prevention Program. Diabetes. 2010 Oct 1;59(10):2672–81. https://doi.org/10.2337/db10-0543
Zhou K, Donnelly LA, Kimber CH, Donnan PT, Doney ASF, Leese G, et al. Reduced-function SLC22A1 polymorphisms encoding organic cation transporter 1 and glycemic response to metformin: a GoDARTS study. Diabetes. 2009 Jun 1;58(6):1434–9. https://doi.org/10.2337/db08-0896
Christensen MMH, Brasch-Andersen C, Green H, Nielsen F, Damkier P, Beck-Nielsen H, et al. The pharmacogenetics of metformin and its impact on plasma metformin steady-state levels and glycosylated hemoglobin A1c. Pharmacogenet Genomics. 2011 Dec;21(12):837–50. https://doi.org/10.1097/FPC.0b013e32834c0010
Rajman I, Knapp L, Hanna I. Genetic diversity in drug transporters: impact in African populations. Clin Transl Sci. 2020 Sep;13(5):848–60. https://doi.org/10.1111/cts.12769
Hennig S, Naiker S, Reddy T, Egan D, Kellerman T, Wiesner L, et al. Effect of SLCO1B1 polymorphisms on rifabutin pharmacokinetics in African HIV-infected patients with tuberculosis. Antimicrob Agents Chemother. 2015 Oct 19;60(1):617–20. https://doi.org/10.1128/AAC.01195-15
Pritchard D, Patel JN, Stephens LE, McLeod HL. Comparison of FDA table of pharmacogenetic associations and Clinical Pharmacogenetics Implementation Consortium guidelines. Am J Health Syst Pharm. 2022 Jun 7;79(12):993–1005. https://doi.org/10.1093/ajhp/zxac064
Wen C, Yee S, Liang X, Hoffmann T, Kvale M, Banda Y, et al. Genome-wide association study identifies ABCG2 (BCRP) as an allopurinol transporter and a determinant of drug response. Clin Pharmacol Ther. 2015 May;97(5):518–25. https://doi.org/10.1002/cpt.89
Roberts RL, Wallace MC, Phipps-Green AJ, Topless R, Drake JM, Tan P, et al. ABCG2 loss-of-function polymorphism predicts poor response to allopurinol in patients with gout. Pharmacogenomics J. 2017 Mar;17(2):201–3. https://doi.org/10.1038/tpj.2015.101
Radtke S, Zolk O, Renner B, Paulides M, Zimmermann M, Möricke A, et al. Germline genetic variations in methotrexate candidate genes are associated with pharmacokinetics, toxicity, and outcome in childhood acute lymphoblastic leukemia. Blood. 2013 Jun 27;121(26):5145–53. https://doi.org/10.1182/blood-2013-01-480335
Ramsey LB, Panetta JC, Smith C, Yang W, Fan Y, Winick NJ, et al. Genome-wide study of methotrexate clearance replicates SLCO1B1. Blood. 2013 Feb 7;121(6):898–904. https://doi.org/10.1182/blood-2012-08-452839
Treviño LR, Shimasaki N, Yang W, Panetta JC, Cheng C, Pei D, et al. Germline genetic variation in an organic anion transporter polypeptide associated with methotrexate pharmacokinetics and clinical effects. J Clin Oncol. 2009 Dec 10;27(35):5972–8. https://doi.org/10.1200/JCO.2008.20.4156
Matthaei J, Kuron D, Faltraco F, Knoch T, Dos Santos Pereira J, Abu Abed M, et al. OCT1 mediates hepatic uptake of sumatriptan and loss-of-function OCT1 polymorphisms affect sumatriptan pharmacokinetics. Clin Pharmacol Ther. 2016 Jun 12;99(6):633–41. https://doi.org/10.1002/cpt.317
Tzvetkov MV, Matthaei J, Pojar S, Faltraco F, Vogler S, Prukop T, et al. Increased systemic exposure and stronger cardiovascular and metabolic adverse reactions to fenoterol in individuals with heritable OCT1 deficiency. Clin Pharmacol Ther. 2018 May 8;103(5):868–78. https://doi.org/10.1002/cpt.812
Giacomini KM, Balimane PV, Cho SK, Eadon M, Edeki T, Hillgren KM, et al. International Transporter Consortium commentary on clinically important transporter polymorphisms. Clin Pharmacol Ther. 2013 Jul;94(1):23–6. https://doi.org/10.1038/clpt.2013.12
Tsamandouras N, Dickinson G, Guo Y, Hall S, Rostami-Hodjegan A, Galetin A, et al. Development and application of a mechanistic pharmacokinetic model for simvastatin and its active metabolite simvastatin acid using an integrated population PBPK approach. Pharm Res. 2015 Jun 2;32(6):1864–83. https://doi.org/10.1007/s11095-014-1581-2
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 authors

This work is licensed under a Creative Commons Attribution 4.0 International License.
