Influence of SLCO1B3 Polymorphisms on Pharmacodynamics of Mycophenolate Mofetil in Lupus Nephritis Patients

OBJECTIVE  To investigate the effect of polymorphisms of solute carrier organic anion transporter family, member 1B3(SLCO1B3) gene on the pharmacodynamics of mycophenolate mofetil(MMF) in patients with lupus nephritis.

METHODS  Patients with lupus nephritis who were treated in Jieyang People’s Hospital from September 2019 to April 2021 were selected. All subjects were treated with MMF for at least 12 months, or discontinued due to poor efficacy. The efficacy of MMF was evaluated. The SLCO1B3 334T>G/699G>A(rs4149117/rs7311358) genotype was detected using Agena MassARRAY^®, and the correlation between gene polymorphisms and MMF pharmacodynamics was analyzed using SPSS 25.0 software.

RESULTS  The genotype frequencies of SLCO1B3 334T>G/699G>A were in Hardy-Weinberg equilibrium. The probability of poor MMF treatment effect of 334GG/699AA carriers was significantly higher than that of 334TT/699AA and 334TG/699GA carriers(P<0.001); Logistic regression showed that both 334GG/699AA and urine protein>2.5 g·(24 h)⁻¹ were the risk factors for poor MMF treatmentOR=4.038(1.731, 9.420), P<0.001; OR=4.157(1.705, 10.137), P=0.002. Combined analysis showed that patients with both 334GG/699AA genotype and urine protein>2.5 g·(24 h)⁻¹ were at higher risk for poor efficacyOR=8.563(3.301, 22.216), P<0.001.

CONCLUSION  SLCO1B3 334T>G/699G>A is related to the efficacy of MMF treating lupus nephritis, and 334GG/699AA carriers are more likely to result in poor efficacy.