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

Qing Shu,1,* Qingqing Fan,1,* Bingzhu Hua,2 Hang Liu,1 Shiying Wang,2 Yunxing Liu,1 Yao Yao,1 Han Xie,1 Weihong Ge1 1Department of Pharmacy, Nanjing Drum Tower Hospital, Nanjing, 210008, People’s Republic of China; 2Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Nanjing, 210008, People’s Republic of China*These authors contributed equally to this workCorrespondence: Weihong GeDepartment of Pharmacy, Nanjing Drum Tower Hospital, Nanjing, 210008, People’s Republic of ChinaEmail 6221230@sina.comIntroduction: 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 C0), 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 C0/d (p=0.003), in which patients with the CC type showed a higher MPA C0/d than patients with the TT type (p=0.001) or the CT type (p=0.000). No significant differences were found in MPA C0/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 C0/d and anemia. IMPDH1 − 106G>A was significantly related to infections. UGT2B7 802C>T was significantly related to Pneumocystis carinii pneumonia infection.Keywords: mycophenolic acid, gene polymorphisms, adverse drug reactions, infections, anemia, autoimmune diseases