Influence of SLCO1B1 521T>C, UGT2B7 802C>T and IMPDH1 −106G>A Genetic Polymorphisms on Mycophenolic Acid Levels and Adverse Reactions in Chinese Autoimmune Disease Patients

Abstract

Introduction: Mycophenolate mofetil (MMF), a new type of immunosuppressant, has emerged as a frontline agent for treating autoimmune diseases. Mycophenolic acid (MPA) is an active metabolite of MMF. MPA exposure varies greatly among individuals, which may lead to adverse drug reactions such as gastrointestinal side effects, infection, and leukopenia. Genetic factors play an important role in the variation of MPA levels and its side effects. Although many published studies have focused on MMF use in patients after organ transplant, studies that examine the use of MMF in patients with autoimmune diseases are still lacking. Methods: This study will not only explore the genetic factors affecting MPA levels and adverse reactions but also investigate the relationships between UGT1A9 −118(dT)9/10, UGT1A9 -1818T>C, UGT2B7 802C>T, SLCO1B1 521T>C, SLCO1B3 334T>G, IMPDH1 −106G>A and MPA trough concentration (MPA C 0 ), along with adverse reactions among Chinese patients with autoimmune diseases. A total of 120 patients with autoimmune diseases were recruited. The MPA trough concentration was detected using the enzyme multiplied immunoassay technique (EMIT). Genotyping was performed using a real-time polymerase chain reaction (PCR) system and validated allelic discrimination assays. Clinical data were collected for the determination of side effects. Results: SLCO1B1 521T>C demonstrated a significant association with MPA C 0 /d (p=0.003), in which patients with the CC type showed a higher MPA C 0 /d than patients with the TT type (p=0.001) or the CT type (p=0.000). No significant differences were found in MPA C 0 /d among the other SNPs. IMPDH1 −106G>A was found to be significantly related to infections (p=0.006). Subgroup analysis revealed that UGT2B7 802C>T was significantly related to Pneumocystis carinii pneumonia infection (p=0.036), while SLCO1B1 521T>C was associated with anemia (p=0.029). Conclusion:For Chinese autoimmune disease patients, SLCO1B1 521T>C was correlated with MPA C 0 /d and anemia. IMPDH1 −106G>A was significantly related to infections. UGT2B7 802C>T was significantly related to Pneumocystis carinii pneumonia infection.

Genetic Polymorphisms and the Clinical Response to Systemic Lupus Erythematosus Treatment Towards Personalized Medicine

“…A study on the effect of genetic polymorphism of transporter genes and associated functional alterations in drug transport showed that 12 SLCO transporter genes (OATP proteins) with different tissue expression profiles have been identified (NAKANISHI and TAMAI, 2012). Another study on autoimmune disease has a result that SLCO1B1 521T > C demonstrated a significant association with MMF, patients with Cytocine-Cytosine (CC) genotype showed a higher blood concentration level than the Thymine-Thymine (TT) genotype or the Cytosine-Thymine (CT) genotype (Shu et al, 2021). But, study on LN patients, MMF 12-h post-dose is related to renal flare, infection, and anemia, without significant association between genetic polymorphism of OATP rs7311358, and rs4149117, to the blood level of MMF (Yap et al, 2020).…”