PERSONALIZED MEDICINE IN GOUT TREATMENT

Nguyễn Thu Hiền; Hoàng Thị Thu Yến; Đỗ Hà Thanh

doi:10.34238/tnu-jst.10372

PERSONALIZED MEDICINE IN GOUT TREATMENT

About this article

Received: 13/05/24 Revised: 17/06/24 Published: 17/06/24

Authors

1. Nguyen Thu Hien , TNU - University of Medicine and Pharmacy
2. Hoang Thi Thu Yen, TNU - University of Sciences
3. Do Ha Thanh, Thai Nguyen National Hospital

Abstract

In gout treatment, celecoxib is commonly used to treat inflammation, fever and pain while allopurinol, lesinurad and pegloticase are prescribed to reduce blood uric acid levels. CYP2C9*2 and CYP2C9*3 of CYP2C9 gene, HLA-B*58:01 of HLA-B gene and some varriants causing G6PD deficiency (Viangchan, Canton…) are related to adverse reactions when gout treatment using above drugs. In this study, we analyzed pathological characteristics, method of gout treatment, distribution of CYP2C9*2, CYP2C9*3, HLA-B*58:01, Viangchan variants and the relationship with the adverse reactions occurring during gout treatment. Analysis results suggested that celecoxib and lesinurad are primarily metabolized by CYP2C9. CYP2C9*2 and CYP2C9*3 reducing CYP2C9 activity causes a serious risk for cardiovascular and gastrointestinal tract when using celecoxib, while lesinurad causing cardiovascular and kidney problems. People carrier HLA-B*58:01 or G6PD deficiency are recommended not to use allopurinol and pegloticase due to causing severe cutaneous adverse reactions, hemolysis and methemoglobinemia which can lead to death. CYP2C9*3, HLA-B*58:01 and Viangchan variants account for a large proportion in Vietnamese people and Asian countries. These results are the basis for constructive research personalized medical treatment to optimize treatment effectiveness and improve the quality of life for gout patients.

Keywords

Gout; CYP2C9; CYP2C9*3; HLA-B; HLA-B*58; G6PD deficiency; Viangchan variant; Personalized medicine

Full Text:

PDF (Tiếng Việt)

References

[1] B. B. Spear, M. Heath-Chiozzi, and J. Huff, "Clinical application of pharmacogenetics," Trends in Molecular Medicine, vol. 7, no. 5, p. 201-4, 2001.

[2] M. Pirmohamed, S. James, S. Meakin, C. Green, A. K. Scott, T. J. Walley, K. Farrar, B. K. Park, and A. M. Breckenridge, "Adverse drug reactions as cause of admission to hospital: prospective analysis of 18 820 patients," British medical journal, vol. 329, no. 7456, p. 15-9, 2004.

[3] H. M. Dunnenberger, K. R. Crews, J. M. Hoffman, K. E. Caudle, U. Broeckel, S. C. Howard, R. J. Hunkler, T. E. Klein, W. E. Evans, and M. V. Relling, "Preemptive clinical pharmacogenetics implementation: current programs in five US medical centers," Annual review of pharmacology and toxicology, vol. 55, no. p. 89-106, 2015.

[4] Z. W. Zhou, X. W. Chen, K. B. Sneed, Y. X. Yang, X. Zhang, Z. X. He, K. Chow, T. Yang, W. Duan, and S. F. Zhou, "Clinical association between pharmacogenomics and adverse drug reactions," Drugs, vol. 75, no. 6, p. 589-631, 2015.

[5] O. Osanlou, M. Pirmohamed, and A. K. Daly, "Pharmacogenetics of Adverse Drug Reactions," Journal of advanced clinical pharmacology, vol. 83, pp. 155-190, 2018.

[6] K. K. Reynolds, D. L. Pierce, F. Weitendorf, and M. W. Linder, "Avoidable drug-gene conflicts and polypharmacy interactions in patients participating in a personalized medicine program," Journal of Personalized Medicine, vol. 14, no. 3, pp. 221-233, 2017.

[7] Thu Ky, "Causes, symptoms and consequences of gout," (in Vietnamese), 2021. [Online]. Available: https://vnexpress.net/nguyen-nhan-trieu-chung-va-hau-qua-cua-benh-gout-4357255.html [Accessed Feb. 08, 2024].

[8] L. Dean, "Lesinurad Therapy and CYP2C9 Genotype," 2019. [Online]. Available: https://www.ncbi.nlm.nih.gov/books/NBK537366/ [Accessed Oct. 15, 2023].

[9] L. Dean and M. Kane, "Allopurinol therapy and HLA-B* 58: 01 genotype," 2020. [Online]. Available: https://europepmc.org/article/nbk/nbk127547 [Accessed 16/10/2023].

[10] L. Dean and M. Kane, "Celecoxib therapy and CYP2C9 genotype," 2021. [Online]. Available: https://www.ncbi.nlm.nih.gov/books/NBK379478/ [Accessed Oct. 16, 2023].

[11] L. Dean and M. Kane, "Pegloticase therapy and G6PD genotype," 2020. [Online]. Available: https://www.ncbi.nlm.nih.gov/books/NBK562620/ [Accessed Oct. 16, 2023].

[12] M. P. Victoria, A. S. Stuart, P. Munir, E. Bernard, S. K. Megan, L. Brandi, and J. M. Adriana, "Medical Genetics Summaries, Last Updated: December 17, 2021," 2021. [Online]. Available: https://www.ncbi.nlm.nih.gov/books/NBK61999/ [Accessed Oct. 12, 2023].

[13] M. Dehlin, L. Jacobsson, and E. Roddy, "Global epidemiology of gout: prevalence, incidence, treatment patterns and risk factors," Nature Reviews Rheumatology, vol. 16, no. 7, p. 380-390, 2020.

[14] M. James and B. Stella, "Everything you need to know about gout," 2021. [Online]. Available: https://www.medicalnewstoday.com/articles/144827 [Accessed Dec. 22, 2023].

[15] Nguyen Thi Ngoc Lan, "Gout disease," in Internal medicine musculoskeletal pathology (in Vietnamse). Ha Noi: Medical Publishing House, pp. 187-21, 2015.

[16] K. L. Rock, H. Kataoka, and J.-J. Lai, "Uric acid as a danger signal in gout and its comorbidities," Nature Reviews Rheumatology, vol. 9, no. 1, pp. 13-23, 2013.

[17] MSD manual, "Gout Disease, Arcording Lawrence M. Ryan , MD, Medical College of Wisconsin (in Vietnamse)," 2015. [Online]. Available: https://www.msdmanuals.com [Accessed 15/02/2024].

[18] Clinical Reference, "Gout," 2024. [Online]. Available: https://clinref.com/rheumatology/gout/ [Accessed Nov. 12, 2023].

[19] A. Gupta, L. Zheng, V. Ramanujam, and J. Gallagher, "Novel use of pharmacogenetic testing in the identification of CYP2C9 polymorphisms related to NSAID-induced gastropathy," Pain Medicine, vol. 16, no. 5, pp. 866-869, 2015.

[20] A. Isvoran, M. Louet, D. L. Vladoiu, D. Craciun, M.-A. Loriot, B. O. Villoutreix, and M. A. Miteva, "Pharmacogenomics of the cytochrome P450 2C family: impacts of amino acid variations on drug metabolism," Drug Discovery Today, vol. 22, no. 2, pp. 366-376, 2017.

[21] D. Van Booven, S. Marsh, H. McLeod, M. W. Carrillo, K. Sangkuhl, T. E. Klein, and R. B. Altman, "Cytochrome P450 2C9-CYP2C9," Pharmacogenetics Genomics, vol. 20, no. 4, pp. 277-281, 2010.

[22] R. Liu, C. Gong, L. Tao, W. Yang, X. Zheng, P. Ma, and L. Ding, "Influence of genetic polymorphisms on the pharmacokinetics of celecoxib and its two main metabolites in healthy Chinese subjects," European Journal of Pharmaceutical Sciences, vol. 79, pp. 13-19, 2015.

[23] S.-H. Kim, D.-H. Kim, J.-Y. Byeon, Y.-H. Kim, D.-H. Kim, H.-J. Lim, C.-M. Lee, S. S. Whang, C.-I. Choi, and J.-W. Bae, "Effects of CYP2C9 genetic polymorphisms on the pharmacokinetics of celecoxib and its carboxylic acid metabolite," Archives of pharmacal research, vol. 40, pp. 382-390, 2017.

[24] Y.-H. Kim, P. Kang, C. K. Cho, E. H. Jung, H.-J. Park, Y. J. Lee, J. W. Bae, C.-G. Jang, and S.-Y. Lee, "Physiologically based pharmacokinetic (PBPK) modeling for prediction of celecoxib pharmacokinetics according to CYP2C9 genetic polymorphism," Archives of pharmacal research, vol. 44, pp. 713-724, 2021.

[25] A. M. Abeles, "Lesinurad in combination with allopurinol: risk without reward? Comment on the article by Saag et al," Arthritis Rheumatology, vol. 69, no. 5, pp. 1122-1122, 2017.

[26] T. Bardin, R. T. Keenan, P. P. Khanna, J. Kopicko, M. Fung, N. Bhakta, S. Adler, C. Storgard, S. Baumgartner, and A. So, "Lesinurad in combination with allopurinol: a randomised, double-blind, placebo-controlled study in patients with gout with inadequate response to standard of care (the multinational CLEAR 2 study)," Annals of the rheumatic diseases, vol. 76, no. 5, pp. 811-820, 2017.

[27] J. A. Singh, "Lesinurad combination therapy with allopurinol in gout: do CLEAR studies make the treatment of gout clearer?," Annals of the rheumatic diseases, vol. 76, no. 5, pp. 779-781, 2017.

[28] X. Zhang, H. Ma, C. Hu, B. Yu, W. Ma, Z. Wu, X. Luo, H. Zou, and M. Guan, "Detection of HLA-B* 58: 01 with TaqMan assay and its association with allopurinol-induced sCADR," Clinical Chemistry Laboratory Medicine, vol. 53, no. 3, pp. 383-390, 2015.

[29] X. Zhang, H. Ma, C. Hu, B. Yu, W. Ma, Z. Wu, X. Luo, H. Zou, M. J. C. C. Guan, and L. Medicine, "Detection of HLA-B* 58: 01 with TaqMan assay and its association with allopurinol-induced sCADR," Clinical Chemistry Laboratory Medicine, vol. 53, no. 3, pp. 383-390, 2015.

[30] C.-H. Lin, J.-K. Chen, T.-M. Ko, C.-Y. Wei, J.-Y. Wu, W.-H. Chung, S.-Y. Chen, Y.-D. Liao, S.-I. Hung, and Y.-T. Chen, "Immunologic basis for allopurinol-induced severe cutaneous adverse reactions: HLA-B* 58: 01-restricted activation of drug-specific T cells and molecular interaction," Journal of Allergy Clinical Immunology, vol. 135, no. 4, pp. 1063-1065, 2015.

[31] R. Pavlos, S. Mallal, D. Ostrov, S. Buus, I. Metushi, B. Peters, and E. Phillips, "T cell–mediated hypersensitivity reactions to drugs," Annual review of medicine, vol. 66, pp. 439-454, 2015.

[32] W. J. Pichler, A. Beeler, M. Keller, M. Lerch, S. Posadas, D. Schmid, Z. Spanou, A. Zawodniak, and B. Gerber, "Pharmacological interaction of drugs with immune receptors: the pi concept," Allergology International, vol. 55, no. 1, pp. 17-25, 2006.

[33] J. Yun, M. J. Marcaida, K. K. Eriksson, H. Jamin, S. Fontana, W. J. Pichler, and D. Yerly, "Oxypurinol directly and immediately activates the drug-specific T cells via the preferential use of HLA-B* 58: 01," The Journal of Immunology, vol. 192, no. 7, pp. 2984-2993, 2014.

[34] Z.-h. Cao, Z.-y. Wei, Q.-y. Zhu, J.-y. Zhang, L. Yang, S.-y. Qin, L.-y. Shao, Y.-t. Zhang, J.-k. Xuan, and Q.-l. Li, "HLA-B* 58: 01 allele is associated with augmented risk for both mild and severe cutaneous adverse reactions induced by allopurinol in Han Chinese," Pharmacogenomics, vol. 13, no. 10, pp. 1193-1201, 2012.

[35] T.-M. Ko, C.-Y. Tsai, S.-Y. Chen, K.-S. Chen, K.-H. Yu, C.-S. Chu, C.-M. Huang, C.-R. Wang, C.-T. Weng, and C.-L. Yu, "Use of HLA-B* 58: 01 genotyping to prevent allopurinol induced severe cutaneous adverse reactions in Taiwan: national prospective cohort study," British medical journal, vol. 351, 2015, doi: 10.1136/bmj.h4848.

[36] C. Lonjou, N. Borot, P. Sekula, N. Ledger, L. Thomas, S. Halevy, L. Naldi, J.-N. Bouwes-Bavinck, A. Sidoroff, and C. De Toma, "A European study of HLA-B in Stevens–Johnson syndrome and toxic epidermal necrolysis related to five high-risk drugs," Pharmacogenetics Genomics, vol. 18, no. 2, pp. 99-107, 2008.

[37] H. J. Park, Y. J. Kim, D. H. Kim, J. Kim, K. H. Park, J.-W. Park, and J.-H. Lee, "HLA allele frequencies in 5802 Koreans: varied allele types associated with SJS/TEN according to culprit drugs," Yonsei medical journal, vol. 57, no. 1, pp. 118, 2016.

[38] S.-I. Hung, W.-H. Chung, L.-B. Liou, C.-C. Chu, M. Lin, H.-P. Huang, Y.-L. Lin, J.-L. Lan, L.-C. Yang, and H.-S. Hong, "HLA-B* 5801 allele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol," Proceedings of the National Academy of Sciences, vol. 102, no. 11, pp. 4134-4139, 2005.

[39] W. Tassaneeyakul, T. Jantararoungtong, P. Chen, P.-Y. Lin, S. Tiamkao, U. Khunarkornsiri, P. Chucherd, P. Konyoung, S. Vannaprasaht, and C. Choonhakarn, "Strong association between HLA-B* 5801 and allopurinol-induced Stevens–Johnson syndrome and toxic epidermal necrolysis in a Thai population," Pharmacogenetics Genomics, vol. 19, no. 9, pp. 704-709, 2009.

[40] M. Tohkin, N. Kaniwa, Y. Saito, E. Sugiyama, K. Kurose, J. Nishikawa, R. Hasegawa, M. Aihara, K. Matsunaga, and M. Abe, "A whole-genome association study of major determinants for allopurinol-related Stevens–Johnson syndrome and toxic epidermal necrolysis in Japanese patients," The pharmacogenomics journal, vol. 13, no. 1, pp. 60-69, 2013.

[41] H.-R. Kang, Y. K. Jee, Y.-S. Kim, L. C. Hwa, J.-W. Jung, S. H. Kim, H.-W. Park, Y.-S. Chang, I.-J. Jang, S.-H. Cho, K.-U. Min, S.-H. Kim, and W. L. Kyung, "Positive and negative associations of HLA class I alleles with allopurinol-induced SCARs in Koreans," Pharmacogenetics Genomics, vol. 21, no. 5, pp. 303-307, 2011.

[42] D. E. Low, A. F. Nurul-Aain, W. C. Tan, J. J. Tang, M. F. Bakhtiar, S. Murad, C. C. Chang, C. L. Too, and M. M. Tang, "HLA-B* 58: 01 association in allopurinol-induced severe cutaneous adverse reactions: the implication of ethnicity and clinical phenotypes in multiethnic Malaysia," Pharmacogenetics Genomics, vol. 30, no. 7, pp. 153-160, 2020.

[43] T. Tse, B. Wu, S. Vagholkar, and S. Willcock, "Allopurinol for gout: Consider the case for limited HLA-B 5801 screening," Australian Journal of General Practice, vol. 51, no. 10, p. 813-814, 2022.

[44] H. Matsuoka, D. T. V. Thuan, H. van Thien, T. Kanbe, A. Jalloh, M. Hirai, M. Arai, and F. Kawamoto, "Seven different glucose-6-phosphate dehydrogenase variants including a new variant distributed in Lam Dong Province in southern Vietnam," Acta Medica Okayama, vol. 61, no. 4, pp. 213-219, 2007.

[45] I. S. Tantular and F. Kawamoto, "Distribution of G6PD deficiency genotypes among Southeast Asian populations," Tropical Medicine Health, vol. 49, no. 1, pp. 1-7, 2021.

[46] S. S. Lee, K.-M. Kim, H. Thi-Le, S.-S. Yea, I.-J. Cha, and J.-G. Shin, "Genetic polymorphism of CYP2C9 in a Vietnamese Kinh population," Therapeutic drug monitoring, vol. 27, no. 2, p. 208-210, 2005.

[47] P.T.T, "Research on genetic diversity CYP2C9, CYP2C19 and CYP2D6 gene in healthy Vietnamese and breast cancer patients (in Vietnamese)," 2021. [Online]. Available: https://www.vista.gov.vn/news/ket-qua-nghien-cuu-trien-khai/nghien-cuu-da-dang-di-truyen-cac-gen-cytochrome-450-cyp2c9-cyp2c19-va-cyp2d6-tren-cac-nhom-nguoi-viet-nam-khoe-manh-va-benh-nhan-ung-thu-vu-4370.html [Accessed Feb. 11, 2024].

[48] N. P. Vu, T. T. H. Ma, N. T. B. Tran, H. T. T. Huynh, T. D. Nguyen, D. T. Nguyen, H. Van Nong, M. T. M. Lee, and H. H. Nguyen, "Polymorphic analysis of CYP2C9 gene in Vietnamese population," Molecular biology reports, vol. 45, no. 5, pp. 893-900, 2018.

[49] B. Hoa, N. Hang, K. Kashiwase, J. Ohashi, L. Lien, T. Horie, J. Shojima, M. Hijikata, S. Sakurada, and M. Satake, "HLA‐A,‐B,‐C,‐DRB1 and‐DQB1 alleles and haplotypes in the Kinh population in Vietnam," Tissue antigens, vol. 71, no. 2, pp. 127-134, 2008.

[50] F. F. González-Galarza, L. Y. Takeshita, E. J. Santos, F. Kempson, M. H. T. Maia, A. L. S. d. Silva, A. L. T. e. Silva, G. S. Ghattaoraya, A. Alfirevic, and A. R. Jones, "Allele frequency net 2015 update: new features for HLA epitopes, KIR and disease and HLA adverse drug reaction associations," Nucleic acids research, vol. 43, no. D1, pp. D784-D788, 2015.

[51] D. V. Nguyen, H. C. Chu, C. Vidal, J. Anderson, N. N. Nguyen, N. Q. T. Do, T. L. Tran, T. N. Nguyen, H. T. T. Nguyen, and R. B. Fulton, "Gene expression profiling in allopurinol-induced severe cutaneous adverse reactions in Vietnamese," Pharmacogenomics, vol. 21, no. 14, pp. 985-994, 2020.

[52] D. A. Do, G. H. L. Le, M. D. Do, and P. T. Mai, "Prevalence of carrying the HLA-B*58:01 allele in patients with skin allergic gout due to allopurinol treatment," Medical Research, vol. 23, no. 1, 2019.

[53] M. D. Do, T. P. Mai, A. D. Do, Q. D. Nguyen, N. H. Le, L. G. H. Le, V. A. Hoang, A. N. Le, H. Q. Le, and P. Richette, "Risk factors for cutaneous reactions to allopurinol in Kinh Vietnamese: results from a case-control study," Arthritis research therapy, vol. 22, no. 1, pp. 1-10, 2020.

[54] D. V. Nguyen, H. C. Chu, C. Vidal, R. B. Fulton, N. N. Nguyen, N. Q. T. Do, T. L. Tran, T. N. Nguyen, H. T. T. Nguyen, and H. H. Chu, "Genetic susceptibilities and prediction modeling of carbamazepine and allopurinol-induced severe cutaneous adverse reactions in Vietnamese," Pharmacogenomics, vol. 22, no. 1, pp. 1-12, 2021.

[55] V. S. Chu, T. H. L. Nguyen, H. T. Tran, X. T. Le, B. K. Nguyen, T. H. N. Le, V. H. Nguyen, N. Q. Tran, V. L. Nguyen, and D. T. Pham, "Predominant HLA Alleles and Haplotypes in Mild Adverse Drug Reactions Caused by Allopurinol in Vietnamese Patients with Gout," Diagnostics, vol. 11, no. 9, p. 1611, 2021.

[56] H. T. Nguyen, J. P. Charlieu, C. T. H. Tran, N. Day, J. J. Farrar, H. T. Tran, and S. J. Dunstan, "Glucose-6-phosphate dehydrogenase (G6PD) mutations and haemoglobinuria syndrome in the Vietnamese population," Malaria journal, vol. 8, no. 1, pp. 1-8, 2009.

[57] G. Bancone, D. Menard, N. Khim, S. Kim, L. Canier, C. Nguong, K. Phommasone, M. Mayxay, S. Dittrich, and M. Vongsouvath, "Molecular characterization and mapping of glucose-6-phosphate dehydrogenase (G6PD) mutations in the Greater Mekong Subregion," Malaria journal, vol. 18, no. 1, pp. 1-15, 2019.

DOI: https://doi.org/10.34238/tnu-jst.10372

Refbacks

There are currently no refbacks.



Remember me