Main Article Content
Abstract
Background: Metformin might be a first therapy for Type 2 diabetes; however, it had a lot of variation in glycemic response. Objective: to analyze the frequency of minor alleles of the OCT1 coding gene (SLC22A1 rs628031) and MATE1 coding gene (SLC47A1 rs2289669) as well as the genotypic variation of the interaction of these two genetic polymorphisms in healthy subjects of Indonesia. Material and Methods: Through inclusion criteria, the study employed an observational descriptive technique with 70 Indonesian Javanese healthy individuals. Subject health information was obtained from the complete blood routine test, serum glutamic oxaloacetic transaminase/ serum glutamic-pyruvic transaminase (SGOT/SGPT), complete urine test, and serum creatinine tests. All data were compared to the normal range. Results: The finding shows that the minor allele frequency on SLC22A1 rs628031 A>G and SLC47A1 rs2289669 G>A respectively at 53% and 36%. There are four SLC22A1 rs628031 and SLC47A1 rs2289669 genetic polymorphism interactions; 16 Wt/Wt (16.75%), 24 Wt/M (25%), 32 M/Wt (33.3%) and 24 M/M (25%). The discovery demonstrates that such minor allele frequencies of the SLC22A1 rs628031 OCT1 and SLC47A1 rs2289669 MATE1 genes in healthy Indonesian subjects are relatively high. The SLC22A1 rs628031 A>G and SLC47A1 rs2289669 G>A respectively at 53% and 36%, almost the same as the minor allele frequencies found in several other Asian countries eg. India, Japan, and China. Conclusions: OCT1 coding genes (SLC22A1 rs628031 A>G) were found more dominant than MATE1 coding genes (SLC47A1 rs2289669 G>A) and both alleles are relatively high in healthy subjects of Indonesia, which can be used as information to explore the consequences of different genes' interactions on the Indonesian pharmacokinetic properties, and the efficacy variations of metformin in Type2 DM patients.
Keywords
Article Details
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
References
- Becker, M. L., Visser, L. E., van Schaik, R. H. N., Hofman, A., Uitterlinden, A. G., & Stricker, B. H. C. (2010). Interaction between polymorphisms in the OCT1 and MATE1 transporter and metformin response. Pharmacogenetics and Genomics, 20(1), 38. doi: 10.1097/FPC.0b013e328333bb11
- Chen, L., Takizawa, M., Chen, E., Schlessinger, A., Segenthelar, J., Choi, J. H., … Giacomini, K. M. (2010). Genetic Polymorphisms in Organic Cation Transporter 1 (OCT1) in Chinese and Japanese Populations Exhibit Altered Function. Journal of Pharmacology and Experimental Therapeutics, 335(1), 42–50. doi: 10.1124/jpet.110.170159
- Christensen, K. H., Röhrs, J., Ward, B., Fer, I., Broström, G., Saetra, Ø., & Breivik, Ø. (2013). Surface wave measurements using a ship-mounted ultrasonic altimeter. Methods in Oceanography, 6, 1–15. doi: 10.1016/j.mio.2013.07.002
- Christensen, M. M. H., Højlund, K., Hother-Nielsen, O., Stage, T. B., Damkier, P., Beck-Nielsen, H., & Brøsen, K. (2015). Steady-state pharmacokinetics of metformin is independent of the OCT1 genotype in healthy volunteers. European Journal of Clinical Pharmacology, 71(6), 691–697. doi: 10.1007/s00228-015-1853-8
- Cook, M. N., Girman, C. J., Stein, P. P., & Alexander, C. M. (2007). Initial monotherapy with either metformin or sulphonylureas often fails to achieve or maintain current glycaemic goals in patients with Type 2 diabetes in UK primary care. Diabetic Medicine, 24(4), 350–358. doi: 10.1111/j.1464-5491.2007.02078.x
- Graham, G. G., Punt, J., Arora, M., Day, R. O., Doogue, M. P., Duong, J. K., … Williams, K. M. (2011). Clinical pharmacokinetics of metformin. Clinical Pharmacokinetics, 50(2), 81–98. doi: 10.2165/11534750-000000000-00000
- Ha Choi, J., Wah Yee, S., Kim, M. J., Nguyen, L., Ho Lee, J., Kang, J.-O., … Giacomini, K. M. (2009). Identification and characterization of novel polymorphisms in the basal promoter of the human transporter, MATE1. Pharmacogenetics and Genomics, 19(10), 770–780. doi: 10.1097/FPC.0b013e328330eeca
- He, R., Zhang, D., Lu, W., Zheng, T., Wan, L., Liu, F., & Jia, W. (2015). SLC47A1 gene rs2289669 G>A variants enhance the glucose-lowering effect of metformin via delaying its excretion in Chinese type 2 diabetes patients. Diabetes Research and Clinical Practice, 109(1), 57–63. doi: 10.1016/j.diabres.2015.05.003
- International Diabetes Federation. (2019). IDF Western Pacific members. Retrieved August 1, 2020, from https://idf.org/our-network/regions-members/western-pacific/members/104-indonesia.html
- Itoda, M., Saito, Y., Maekawa, K., Hichiya, H., Komamura, K., Kamakura, S., … Sawada, J. (2004). Seven novel single nucleotide polymorphisms in the human SLC22A1 gene encoding organic cation transporter 1 (OCT1). Drug Metabolism and Pharmacokinetics, 19(4), 308–312. doi: 10.2133/dmpk.19.308
- Kajiwara, M., Terada, T., Ogasawara, K., Iwano, J., Katsura, T., Fukatsu, A., … Inui, K. (2009). Identification of multidrug and toxin extrusion (MATE1 and MATE2-K) variants with complete loss of transport activity. Journal of Human Genetics, 54(1), 40–46. doi: 10.1038/jhg.2008.1
- Kang, H.-J., Song, I.-S., Shin, H. J., Kim, W.-Y., Lee, C.-H., Shim, J.-C., … Shin, J.-G. (2007). Identification and Functional Characterization of Genetic Variants of Human Organic Cation Transporters in a Korean Population. Drug Metabolism and Disposition, 35(4), 667–675. doi: 10.1124/dmd.106.013581
- Koehler, M. J., & Mishra, P. (2008). Introducing TPCK. In AACTE Committe on Innovation and Technology (Eds), Handbook of Technological Content Knowledge (TPCK) for Educators. New York: Routledge.
- Koepsell, H., Lips, K., & Volk, C. (2007). Polyspecific Organic Cation Transporters: Structure, Function, Physiological Roles, and Biopharmaceutical Implications. Pharmaceutical Research, 24(7), 1227–1251. doi: 10.1007/s11095-007-9254-z
- National Agency of Drug and Food Control. (2015). Pedoman metodologi uji bioekivalensi spesifik zat aktif [A guideline of methodology for testing specific bioequivalence of active substances]. Jakarta: Badan Pengawas Obat dan Makanan Republik Indonesia (BPOM RI).
- Nies, A. T., Damme, K., Kruck, S., Schaeffeler, E., & Schwab, M. (2016). Structure and function of multidrug and toxin extrusion proteins (MATEs) and their relevance to drug therapy and personalized medicine. Archives of Toxicology, 90(7), 1555–1584. doi: 10.1007/s00204-016-1728-5
- Ningrum, V., Ikawati, Z., Sadewa, A., & Ikhsan, M. (2017a). Allele frequencies of two main metformin transporter genes: SLC22A1rs628031A>G and SLC47A1rs2289669G>A among the Javanese Population in Indonesia. CPPM, 15(2). doi: 10.2174/1875692115666170706113120
- Ningrum, V., Ikawati, Z., Sadewa, A., & Ikhsan, R. (2017b). Hubungan antara variasi genetik pada OCT1 dan MATE1 dengan farmakokinetika kadar tunak dan farmakodinamika metformin (Correlation between genetic variation of OCT1 and MATE1 with pharmacokinetic of tunak percentage and pharmacodynamics of metformin) [dissertation]. Yogyakarta: Faculty of Pharmacy, Gajahmada University.
- Rena, G., Hardie, D. G., & Pearson, E. R. (2017). The mechanisms of action of metformin. Diabetologia, 60(9), 1577–1585. doi: 10.1007/s00125-017-4342-z
- Shu, Y., Brown, C., Castro, R. A., Shi, R. J., Lin, E. T., Owen, R. P., … Giacomini, K. M. (2008). Effect of genetic variation in the organic cation transporter 1, OCT1, on metformin pharmacokinetics. Clinical Pharmacology and Therapeutics, 83(2), 273–280. doi: 10.1038/sj.clpt.6100275
- Soelistijo, S. A., Suastika, K., Lindarto, D., Decrol, E., Permana, H., Sucipto, K. W., … Susanto, H. (2019). Pedoman Pengelolaan dan Pencegahan Diabetes Melitus Tipe 2 di Indonesia 2021 [Guidelines for the Management and Prevention of Type 2 Diabetes Mellitus in Indonesia 2021]. Jakarta: PB Perkeni.
- Stocker, S. L., Morrissey, K. M., Yee, S. W., Castro, R. A., Xu, L., Dahlin, A., … Giacomini, K. M. (2013). The effect of novel promoter variants in MATE1 and MATE2 on the pharmacokinetics and pharmacodynamics of metformin. Clinical Pharmacology and Therapeutics, 93(2), 186–194. doi: 10.1038/clpt.2012.210
- Sur, D. (2014). A tale of genetic variation in the human SLC22A1 gene encoding OCT1 among type 2 diabetes mellitus population groups of West Bengal, India. IJRANSS, 2(5), 97–106. doi: 10.4172/1747-0862.C1.010
- Tarasova, L., Kalnina, I., Geldnere, K., Bumbure, A., Ritenberga, R., Nikitina-Zake, L., … Klovins, J. (2012). Association of genetic variation in the organic cation transporters OCT1, OCT2 and multidrug and toxin extrusion 1 transporter protein genes with the gastrointestinal side effects and lower BMI in metformin-treated type 2 diabetes patients. Pharmacogenetics and Genomics, 22(9), 659–666. doi: 10.1097/FPC.0b013e3283561666
- Tkáč, I., Klimčáková, L., Javorský, M., Fabianová, M., Schroner, Z., Hermanová, H., … Tkáčová, R. (2013). Pharmacogenomic association between a variant in SLC47A1 gene and therapeutic response to metformin in type 2 diabetes. Diabetes, Obesity & Metabolism, 15(2), 189–191. doi: 10.1111/j.1463-1326.2012.01691.x
- Toyama, K., Yonezawa, A., Tsuda, M., Masuda, S., Yano, I., Terada, T., … Inui, K.-I. (2010). Heterozygous variants of multidrug and toxin extrusions (MATE1 and MATE2-K) have little influence on the disposition of metformin in diabetic patients. Pharmacogenetics and Genomics, 20(2), 135–138. doi: 10.1097/FPC.0b013e328335639f
- Tzvetkov, M. V., Vormfelde, S. V., Balen, D., Meineke, I., Schmidt, T., Sehrt, D., … Brockmöller, J. (2009). The Effects of Genetic Polymorphisms in the Organic Cation Transporters OCT1, OCT2, and OCT3 on the Renal Clearance of Metformin. Clinical Pharmacology & Therapeutics, 86(3), 299–306. doi: 10.1038/clpt.2009.92
- Xiao, D., Guo, Y., Li, X., Yin, J.-Y., Zheng, W., Qiu, X.-W., … Liu, Z.-Q. (2016). The Impacts of SLC22A1 rs594709 and SLC47A1 rs2289669 Polymorphisms on Metformin Therapeutic Efficacy in Chinese Type 2 Diabetes Patients. International Journal of Endocrinology, 2016, e4350712. doi: 10.1155/2016/4350712
- Yin, O. Q. P., Tomlinson, B., & Chow, M. S. S. (2006). Variability in renal clearance of substrates for renal transporters in chinese subjects. Journal of Clinical Pharmacology, 46(2), 157–163. doi: 10.1177/0091270005283838
- Yoon, H., Cho, H.-Y., Yoo, H.-D., Kim, S.-M., & Lee, Y.-B. (2013). Influences of Organic Cation Transporter Polymorphisms on the Population Pharmacokinetics of Metformin in Healthy Subjects. The AAPS Journal, 15(2), 571–580. doi: 10.1208/s12248-013-9460-z
- Zhou, Y., Ye, W., Wang, Y., Jiang, Z., Meng, X., Xiao, Q., … Yan, J. (2015). Genetic variants of OCT1 influence glycemic response to metformin in Han Chinese patients with type-2 diabetes mellitus in Shanghai. International Journal of Clinical and Experimental Pathology, 8(8), 9533–9542.