SLCO1B3基因多态性对狼疮性肾炎患者吗替麦考酚酯疗效的影响

目的 探讨有机阴离子转运体1B3(solute carrier organic anion transporter family, member 1B3，SLCO1B3)基因多态性对狼疮性肾炎患者吗替麦考酚酯(mycophenolate mofetil，MMF)药效学的影响。方法 以2019年9月—2021年4月于揭阳市人民医院就诊的新确诊的或既往确诊的狼疮性肾炎患者为研究对象。受试者均使用MMF治疗，且总疗程≥12个月，综合评估MMF的疗效。采用Agena MassARRAY^®方法检测受试者SLCO1B3 334T>G/699G>A (rs4149117/rs7311358)基因型，应用SPSS 25.0软件分析基因多态性与MMF药效学的相关性。结果 SLCO1B3 334T>G/699G>A基因型频率符合Hardy-Weinberg 平衡。334GG/699AA携带者MMF疗效差的几率显著高于334TT/699AA和334TG/699GA携带者(P<0.001)；Logistics回归显示334GG/699AA和尿蛋白>2.5 g·(24 h)^-1是MMF疗效差的危险因素[OR=4.038(1.731，9.420)，P<0.001；OR=4.157(1.705，10.137)，P=0.002]。经过联合分析表明，携带334GG/699AA型且尿蛋白>2.5 g·(24 h)^-1的患者疗效差的风险是非334GG/699AA携带者的8.563倍[(3.301，22.216)，P<0.001]。结论 SLCO1B3 334T>G/699G>A与狼疮性肾炎患者MMF疗效有关，334GG/699AA携带者MMF疗效差的可能性更高。

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 treatment[OR=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 efficacy[OR=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.