The Association of UGT1A9 -2152 (C>T) Gene Polymorphism With Allograft Rejection Among Kidney Transplant Rejection Among Kidney Transplant Recipients Receiving Mycophenolic Acid In Indonesia: A Case Control Study

Aqmarina Tamimi, Prof. Dr. apt. Zullies Ikawati; dr. Yulia Wardhani, Sp.PD-KGH.; Prof. Dr. rer. nat. apt. Adam Hermawan, M.Sc.; Dr. Yow Hui Yin

2025 | Tesis | S2 Mag.Farmasi Klinik

Latar belakang: Transplantasi ginjal merupakan salah satu terapi yang penting untuk mengatasi penyakit ginjal kronik tahap akhir. Penggunaan imunosupresan, seperti asam mikofenolat, menjadi standar dalam manajemen resipien transplantasi ginjal untuk mencegah penolakan organ. Namun, efek dari obat tersebut dapat bervariasi di antara individu, sebagian besar disebabkan oleh perbedaan dalam metabolisme obat yang dipengaruhi oleh faktor genetik. Salah satu enzim yang penting dalam metabolisme mikofenolat adalah UDP-glukuronosiltransferase 1A9 (UGT1A9), yang dikodekan oleh gen UGT1A9 -2152 (C>T). Polimorfisme genetik dalam UGT1A9 -2152 (C>T) telah dikaitkan dengan variasi dalam aktivitas enzim, yang dapat memengaruhi metabolisme asam mikofenolat dan akhirnya 

mempengaruhi risiko rejeksi allograft pada resipien transplantasi ginjal.

Tujuan: Penelitian ini bertujuan untuk menyelidiki hubungan antara polimorfisme genetik UGT1A9 -2152 (C>T) dengan kejadian rejeksi allograft pada resipien pasien transplantasi ginjal yang menggunakan asam mikofenolat sebagai bagian dari rejimen imunosupresan mereka. 

Metode: Metode yang akan digunakan meliputi pengumpulan sampel darah dari pasien, analisis polimorfisme genetik UGT1A9 -2152 (C>T) menggunakan Restriction Fragment Length Polymerase (RFLP). Pemantauan tingkat rejeksi organ melalui pemeriksaan klinis dan laboratorium yang ditentukan oleh klinisi. Disain penelitian menggunakan case-control, melibatkan 40 resipien yang telah menjalani transplantasi ginjal di RSUP Dr. Sardjito, rekruitmen pasien dimulai tahun 2017 hingga 2025. Metode statistik yang digunakan dalam penelitian ini meliputi uji Chi-square dan Fisher’s exact test, uji keseimbangan Hardy–Weinberg, uji T, serta perhitungan odds ratio (OR).

Hasil: Distribusi genotipe pada resipien transplantasi ginjal UGT1A9 -2152 (C>T) terindentifikasi sebagai berikut: 73.33% (CC), 26.67% (CT), 0.0% (TT) di kelompok kasus dan 100% (CC), 0.0% (CT), 0.0% (TT) di kelompok kontrol. Terdapat perbedaan yang signifikan pada distribusi genotip (p = 0,015, OR = 0,092, 

95% CI = 0,010–0,879) maupun frekuensi alel (p = 0,017, OR = 0,106, 95% CI = 0,012–0,953) antar kelompok. Penelitian ini menemukan adanya hubungan yang signifikan antara varian genetik UGT1A9 -2152 (C>T) dengan kejadian rejeksi allograft pada resipien transplantasi ginjal di Indonesia

Kata kunci: transplantasi ginjal, mikofenolat mofetil (MMF), UGT1A9 -2152 (C>T), Single Nucleotide Polymorphism (SNP), PCR-RFLP.

Background: Kidney transplantation is an essential therapy to treat end-stage renal disease (ESRD). The use of immunosuppressants, such as mycophenolic acid (MPA), has become standard the standard in managing kidney transplant recipients to prevent organ rejection. However, the effects of these drugs can vary among individuals, largely due to differences in drug metabolism that are influenced by genetic factors. One of the key enzymes in MPA metabolism is UDPglucuronosyltransferase 1A9 (UGT1A9), encoded by the UGT1A9 gene. Genetic polymorphism at position -2152 (C>T) in UGT1A9 has been associated with variations in enzyme activity, which potentially affecting MPA metabolism and ultimately influencing the risk of rejection in kidney transplant recipients.

Objective: This study aimed to investigate the association between UGT1A9 -2152 (C>T) genetic polymorphism and the occurrence of allograft rejection in kidney transplant recipients taking MPA as part of their immunosuppressive regimen. 

Method: Blood samples were collected from recipients, and DNA was isolated for analysis of the UGT1A9 ?2152 (C>T) polymorphism using the Restriction Fragment Length Polymorphism (RFLP) method. The occurrence of allograft rejection was monitored through clinical and laboratory examinations as determined by clinician. A case control study design was used, involving 40 kidney transplant recipients at Dr. Sardjito General Hospital, and the patients recruited from 2017 to 2025. Participants were categorized into a control group (n=25) and case group (n=15). The statistical methods applied in this study included testing for Chi-square and Fisher’s exact tests, Hardy–Weinberg equilibrium, t-test, and calculating odds ratios (ORs).

Results: The genotype distribution of UGT1A9 ?2152 (C>T) were 73.33% (CC), 26.67% (CT), and 0.0% (TT) in the case group, and 100% (CC) in the control group. There were significant differences in genotype distribution (p = 0.015, OR = 0.092, 95% CI = 0.010-0.879) or allele frequency (p = 0.017, OR = 0.106, 95% CI = 0.012-0.953) between groups. The study found that significant association between the UGT1A9 -2152 (C>T) genetic variants and allograft rejection in Indonesian kidney transplant recipients.

Key words: renal transplantation, mycophenolate mofetil (MMF), UGT1A9 -2152 (C>T), Single Nucleotide Polymorphism (SNP), PCR-RFLP.

Kata Kunci : renal transplantation, mycophenolate mofetil (MMF), UGT1A9 -2152 (C>T), Single Nucleotide Polymorphism (SNP), PCR-RFLP.