Abstract:
Objective To investigate the association between Chinese Han refractory lupus nephritis (LN) and cyclophosphamide-metabolizing enzyme gene polymorphism.
Methods From January 2012 to December 2015 in Haikou People′s Hospital, 132 patients with initial SLE were analyzed, including 88 patients in the LN group, and 44 patients in the non-LN group. In the LN group, 46 patients had refractory LN, and 42 patients had non-refractory LN. The CTX metabolic enzyme gene was detected by PCR-RELP method, and the correlation of CYP2C19*2, CYP2C19*3, CYP2B6*4, CYP2C9*3, and CYP3A5 with LN, refractory LN, and non-refractory LN was analyzed by one-way analysis of variance.
Results (1) The frequency distribution of CYP2C19*2, CYP2C19*3, CYP2B6*4, and CYP3A5 accorded with the Hardy-Weinberg equilibrium distribution; (2) Compared with the non-LN group, the LN group had significantly higher levels of serum creatinine (Scr) (t=2.68, P=0.008) and SLEDAI (t=4.07, P≤0.001), but had significantly lower levels of hemoglobin (Hb) (t=-2.368, P=0.019) and serum albumin (ALB) (t=-4.514, P=0.000); (3) One-way analysis of variance showed that the CYP2C19*3 GC carriers in the LN group had significantly higher level of blood urea nitrogen (BUN) compared with those CC and GG carriers [(13.3±13.02) mmol/L and (6.57±5.22) mmol/L and (7.08±6.11) mmol/L, F=5.770, P=0.004]. In the refractory LN group, GC carriers had significantly higher levels of Scr than those CC and GG carriers [(436.22±286.38) μmol/L, (161.7±144.33) μmol/L, (66±19.02)μmol/L, F=8.411, P=0.001]; (4) CYP3A5*3 GG carriers had significantly-increased renal involvement (χ2=6.991, P=0.03). In the refractory LN group, patients with the CYP3A5*3 GG genotype had higher level of Scr (F=0.213, P=0.81), but the difference was not statistically significant.
Conclusion The CYP2C19*3 gene polymorphism of the cyclophosphamide-metabolizing enzyme might have an influence on the treatment efficacy in the the Chinese Han patients with refractory LN, with the GC carriers having less treatment efficacy, and the kidney involvement being more common in the CYP3A5*3 GG genotype carriers.
Key words:
Cyclophosphamide-metabolizing enzyme,
Gene polymorphism,
Systemic lupus erythematosus,
Lupus nephritis
Jun Zhou, Zhen Yang. Association between gene polymorphism of cyclophosphamide-metabolizing enzyme and refractory lupus nephritis in Chinese Han people[J]. Chinese Journal of Kidney Disease Investigation(Electronic Edition), 2019, 08(03): 109-113.