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All Journal Farmaka Althea Medical Journal Jurnal Farmasi Klinik Indonesia The Indonesian Biomedical Journal Indonesian Journal of Rheumatology Indonesian Journal of Obstetrics & Gynecology Science Jurnal Kreativitas PKM Narra J
Laniyati Hamijoyo, Laniyati
Departemen Ilmu Penyakit Dalam Fakultas Kedokteran Universitas Padjadjaran Rumah Sakit Umum Pusat Hasan Sadikin Bandung
Biochemistry, Genetics & Molecular Biology Chemistry Health Professions Immunology & microbiology Materials Science & Nanotechnology Medicine & Pharmacology Nursing Public Health

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GSTA1 gene polymorphisms are associated with cyclophosphamide effectiveness in lupus nephritis patients: A case-control study in Indonesia Indrawijaya, Yen YA.; Artarini, Aluicia A.; Hamijoyo, Laniyati; Iwo, Maria I.
Narra J Vol. 4 No. 3 (2024): December 2024
Publisher : Narra Sains Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.52225/narra.v4i3.1144

Abstract

Glutathione-S-transferase alpha-1 (GSTA1) is an enzyme with high conjugation activity against aldophosphamide, a metabolite of cyclophosphamide and promoter polymorphisms in GSTA1 may influence the cyclophosphamide effectiveness. The aim of this study was to evaluate the effectiveness and side effects of cyclophosphamide in lupus nephritis patients, using GSTA1 variants as predictors. A case-control study was conducted at Hasan Sadikin Hospital, Bandung, Indonesia, involving 100 lupus nephritis patients from February 2023 to January 2024. The PCR-Sanger sequencing was used to genotype five selected single nucleotide polymorphisms (SNPs) in the GSTA1 promoter: -52 A>G, -69 T>C, -513 A>G, -567 G>T, and -631 G>T. The endpoint was assessed after six doses of cyclophosphamide by evaluating renal function, disease activity and side effects. Results indicated that six doses of intravenous cyclophosphamide treatment improved renal function and disease activity in the patients, as evidenced by significant changes in serum creatinine (0.79 vs 0.69 mg/dL), dipstick proteinuria (3.00 vs 1.50), creatinine clearance (98.50 vs 109.50 mL/min), and Modified Systemic Lupus Erythematosus Disease Activity Index 2000 (M-SLEDAI-2K) score (8.61 vs 6.95). The AG genotype at -513 A>G was associated with reduced cyclophosphamide effectiveness (odds ratio (OR): 0.19; 95%CI: 0.19–0.60; p=0.019). The GT genotype at -631 G>T independently increased the progression of anemia (OR: 2.41; 95%CI: 0.26–22.12; p=0.040). This study highlights that the presence of GSTA1 variants affected cyclophosphamide effectiveness in lupus nephritis patients, with heterozygous polymorphisms at -513 (AA to AG) and -631 (TT to GT) predicting reduced effectiveness of cyclophosphamide by enhancing GSTA1 promoter activity, while anemia further exacerbated lupus nephritis disease severity. GSTA1 polymorphism was not associated with the presence of alopecia, amenorrhea, gastrointestinal disorders, and leukopenia during cyclophosphamide therapy.
Co-Authors A Tjandrawati A Tjandrawati A, Muhammad Naufal Achadiyani Achadiyani Achadiyani Adhi Pribadi Afifah, Nadya Nurul Aini, Y H Aini, Yulia Hayatul Alfarish, M Arzan Alfi, Mohammad Abyan Amaylia Oehadian Andiyang R. Diredja Andri Reza Rahmadi Anjalia, Safira Anna Ariane Anna Ariane Anna Tjandrawati Artarini, Aluicia A. Astuti, Intan Widya Aulia Nurlatifah Awalia Awalia Azzahra, Fadhilla Zakya Bambang Setiyohadi Bambang Setiyohadi Bernard Santoso Suryajaya Bethy Suryawathy Hernowo Budi Setiabudiawan Chin Annsha Veimern Coriejati Rita D Nilasari D, H Purbo Dewi Kartika Turbawaty Dewi, Sumartini Dwi Budi Darmawati E Sutedja Edhyana Sahiratmadja Edhyana Sahiratmadja Eka Kurniawan Ellyana Sungkar Endang Sutedja Enrica, M Erica Kwan Yue Fadillah, Viki Faisal Parlindungan Faisal Parlindungan Fajar, Desi Reski Faliq, Muhammad Faza Farid Yudoyono Febyani, M Ferdy Ferdian Gede Kambayana Ghassani, Nadia Gita Guntur Darmawan Guntur Darmawan H Purbo D Habib Burahman Handono Halim Handono Kalim Harry Isbagio Harry Isbagio Hartati Purbo Dharmadji Hartati Purbo Dharmadji Hartati Purbo Dharmadji, Hartati Purbo I Nyoman Suarjana Ignatius Irawan Hidayat Ika Agus Rini Ika Vemilia Warlisti Indrawijaya, Yen YA. Irsan Hasan Ismiana Fatimah Modjaningrat Iwo, Maria I. Kasjmir, Yoga I Kennardi, Gabriel Bagus Lestari, Frida Dwi Lisda Amalia M Arzan Alfarish M Enrica M Febyani Maharani, Khalista Ismaya Malikul Chair Melisa I. Barliana Melisa Intan Barliana, Melisa Intan Modjaningrat, Ismiana Fatimah Mohammad Ghozali Mohammad Ghozali, Mohammad Muhammad Syawal Pratama Muhammad Zafrullah Arifin Mulya Nurmansyah Ardisasmita N Suraya Nadia Gita Ghassani Nadia Gita Ghassani Nadifa, Safira Najirman Najirman Nilasari, D Nita Novita Nita Novita Nur Atik Nur Atik O Suwarsa Ong, Paulus Anam Pande Ketut Kurniari Patrick Philo Paulus Anam Ong Permatasari, Lany Indah Praptama, Suhendra Pratama, Mirza Zaka Pratama, Muhammad Kevin Pratama, Muhammad Syawal Putra, Septian Dwi Putri Vidyaniati Putri, Rahmania Devina Rachmat Gunadi Wachjudi Rachmayati, S Radiyati Umi Partan Rahadian Nugi Sutrisno Rakhma Yanti Hellmi Rakhma Yanti Helmi Ria Bandiara Riardi Pramudiyo Rizky Abdullah RM Suryo Anggoro Rudy Hidayat Rully Hanafi Dahlan Ryan Ardian Saputro S Rachmayati Safira Anjalia Safira Nadifa Santi Andayani Sasfia Candrianita Sasfia Candrianita Septian Dwi Putra Setyorini Irianti Sevline Esthetia Ompusunggu Sevline Esthetia Ompusunggu Shadrina, Siti Azyyati Nur Soeseno Hadi Soeseno Hadi Stefanie Yuliana Usman Stefanie Yuliana Usman Stefanie Yuliana Usman Suhendra Praptama Sulaiman, Aina Zakia Sumariyono Sumartini Dewi Sumartini Dewi Suraya, N Surya Darma Suryana, Bagus Putu Putra Sutedja, E Sutrisno, Rahadian Nugi Suwarsa, O Tear, Alveron Andreas Tina Rostinawati Tjandrawati, A Trinugroho Heri Fadjari, Trinugroho Heri Usman, Stefanie Yuliana Valentine Natasya Moenadi Veimern, Chin Annsha Wahono, Cesarius Singgih Wijaya, Indra Wulansari Manuaba, Ida Ayu Ratih Y H Aini Yoga I Kasjmir Yue, Erica Kwan Yulia Hayatul Aini Yulyani Werdiningsih