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  2. Vol 55, No 3 (2023)
  3. Indrawijaya

Genetic Polymorphisms Associated with Cyclophosphamide Outcome and Risk of Toxicity in Patients with Lupus Nephritis

Yen Yen Ari Indrawijaya, Laniyati Hamijoyo, Aluicia Anita Artarini, Maria Immaculata Iwo

Abstract


A 6-month cyclophosphamide induction therapy followed by maintenance therapy every three months is the first-line treatment for Class III, IV, and V lupus nephritis. Among the 139 single nucleotide polymorphisms (SNPs) associated with cyclophosphamide, four SNPs, namely rs4244285, rs4802101, rs7254579 and rs3957356, are related to the response and risk of toxicity in patients with lupus nephritis. Although pharmacogenetic studies in patients with lupus nephritis (LN) have not been conducted previously in Indonesia, data on rs4244285 are available for several ethnic groups, including Papuans, Bataks, Balinese, Dayaks, Javanese, Bugis, Chinese, Timorese and Malays, even though direct evidence in LN patients is less detectable. However, this can be followed up prior to cyclophosphamide therapy based on the identification of genetic markers. Therefore, clinical studies in patients with lupus nephritis are deemed necessary to evaluate the potential of these markers.


Keywords


Cyclophosphamide; SNP; response; risk of toxicity

References


Mok CC. A Consensus for the Management of Systemic Lupus Erythematosus in Asia. J Clin Rheumatol Immunol. 2021;21:1–6.

Yu F, Haas M, Glassock R, Zhao MH. Redefining lupus nephritis: Clinical implications of pathophysiologic subtypes. Nat Rev Nephrol. 2017;13:483–95.

Tamirou F, Houssiau F. Management of lupus nephritis. J Clin Med. 2021;10:1–11.

Hamijoyo L. The clinical characteristics of systemic lupus erythematosus patients in Indonesia: a cohort registry from an Indonesia-based tertiary referral hospital. Lupus. 2019;1–6. doi:10.1177/0961203319878499.

Chen, W, Tang, X, Liu, Q, Chen, W, Fu, P, Liu, F, L. Short-term outcomes of induction therapy with tacrolimus versus cyclophosphamide for active lupus nephritis: A multicenter randomized clinical trial. Am J Kidney Dis. 2011;57:235–44.

Draft PR, Kdigo. 2023 clinical practice guideline for the management of lupus nephritis confidential: Do not distribute public review draft. (2023).

Mok CC. The Asia-Pacific League of Associations for Rheumatology consensus statements on the management of systemic lupus erythematosus. Lancet Rheumatol. 2021;3:e517–e531.

Teles KA, Medeiros-Souza P, Lima FAC, Araújo BG, Lima RAC. Cyclophosphamide administration routine in autoimmune rheumatic diseases: a review. Rev Bras Reumatol. 2017;57:596–604.

Bobirca A. Evaluation of treatment response in lupus nephritis. Med Mod. 2021;28:389–95.

Delfino J, Dos Santos TA, F. G, Skare TL. Comparison of lupus patients with early and late onset nephritis: a study in 71 patients from a single referral center. Adv. Rheumatol. 2020;60:5.

Barber MR, W, et al. Global epidemiology of systemic lupus erythematosus. Nat Rev Rheumatol. 2021;17:515–32.

Wang H, N, et al. The influence of GSTA1 polymorphism to the response to intravenous cyclophosphamide therapy in the lupus nephritis patients. Lupus Open Access. 2016;01:4–6.

Obrișcă B, Sorohan B, Tuță L, Ismail G. Advances in lupus nephritis pathogenesis: From bench to bedside. Int J Mol Sci. 2021;22.

De Zubiria Salgado, Herrera-Diaz C. Lupus nephritis: An overview of recent findings. Autoimmune Dis. 2012;1.

Anders H J. Lupus nephritis. Nat Rev Dis Prim. 2020; 6:1–25.

Mok CC, Kwok RCL, Yip PSF. Effect of renal disease on the standardized mortality ratio and life expectancy of patients with systemic lupus erythematosus. Arthritis Rheum. 2013;65:2154–60.

Malsagova KA. Pharmacogenetic testing: A tool for personalized drug therapy optimization. Pharmaceutics. 2020;12:1–23.

Kumaraswami, K. et al. Epistatic interactions among CYP2C19-2, CYP3A4 and GSTP1 on the cyclophosphamide therapy in lupus nephritis patients. Pharmacogenomics. 2017;18:1413–25.

Wang HN. The GSTA1 polymorphism and cyclophosphamide therapy outcomes in lupus nephritis patients. Clin Immunol. 2015;160:342–8.

Shu W. Genetic markers in CYP2C19 and CYP2B6 for prediction of cyclophosphamide’s 4-hydroxylation, efficacy and side effects in Chinese patients with systemic lupus erythematosus. Br J Clin Pharmacol. 2015;81:327–40.

Ngamjanyaporn P. Pharmacogenetics of cyclophosphamide and CYP2C19 polymorphism in Thai systemic lupus erythematosus. Rheumatol Int. 2011;31:1215–8.

Jiang YP. Comparative efficacy and safety of mycophenolate mofetil and cyclophosphamide in the induction treatment of lupus nephritis: A systematic review and meta-analysis. Medicine (Baltimore). 2020;99:e22328.

Sigdel MR, Kafle MP, Shah DS. Outcome of low dose cyclophosphamide for induction phase treatment of lupus nephritis, a single center study. BMC Nephrol. 2016;17:1–7.

Hajdinák P. Genetic polymorphism of GSTP-1 affects cyclophosphamide treatment of autoimmune diseases. Molecules. 2020;25:1–12.

U.S. Department of Health and Human Services. Common Terminology Criteria for Adverse Events (CTCAE).v.5.0. Cancer Therapy Evaluation Program (CTEP) http://upen.terengganu.gov.my/index.php/2017 (2017).

Desta Z. PharmVar GeneFocus: CYP2B6. Clin Pharmacol Ther. 2021;110:82–97.

Alamilla Sanchez ME, Alcala-Salgado MA, Alonso-Bello CD, Fonseca Gonzalez GT. Mechanism of action and efficacy of immunosupressors in lupus nephritis. Int J Nephrol Renovasc Dis. 2021;14:441–58.

Quan XY. Revisited cyclophosphamide in the treatment of lupus nephritis. Biomed Res Int. 2022.

Rashighi M, Harris JE. 乳鼠心肌提取 HHS Public Access. Physiol Behav. 2017;176:139–48.

Iqubal A. Molecular mechanism involved in cyclophosphamide-induced cardiotoxicity: Old drug with a new vision. Life Sci. 2019;218:112–31.

Lang T. Extensive genetic polymorphism in the human CYP2B6 gene with impact on expression and function in human liver. Pharmacogenetics. 2001;11:399–415.

Singh RR, Reindl KM. Glutathione S-transferases in cancer. Antioxidants. 2021;10:1–25.

Miftahussurur M. CYP2C19 polymorphisms in indonesia: Comparison among ethnicities and the association with clinical outcomes. Biology (Basel). 2021;10:1–12.

Hayati L, Yoga FS. Prevalensi polimorfisme gen CYP2C19 dan pengaruhnya dalam metabolisme omeprazole sebagai prediktor intoksikasi obat pada etnis melayu di sumatera selatan abstrak gen didapatkan selama perkembangan evolusi melalui berbagai. Sriwij J Med. 2018;1:108–14.

Utami PR, Rochmawati ID, Fandinata SS. Polimorfisme CYP2C19*2 terhadap agregasi platelet dan kejadian kardiovaskular pada pasien penyakit jantung koroner. J Ilm Manuntung. 2021;7:21–31.

Clark DP, Pazdernik N. Biotechnology. Second Edition. Second Edition. Vol. 11. New York: Elsevier; 2016.

Cotton MR. Pharm Var GeneFocus: CYP2C19. Clin Pharmacol Ther. 2021;109:352–66.


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