论文部分内容阅读
目的 探讨系统性红斑狼疮(SLE)患者体内细胞色素P450(CYP)450 3A4与腺苷三磷酸结合转运蛋白G超家族成员2(ABCG2)基因多态性对羟氯喹(HCQ)血药浓度的影响.方法 收集46例系统性红斑狼疮患者羟氯喹全血药物浓度测定数据,通过Sanger法测定患者的CYP3A4*1G(rs2242480)与ABCG2(rs2231142)基因型,分析每个基因的多态性对羟氯喹血药浓度的影响.结果 患者CYP3A4*1G各基因型组中,野生纯合子(*1/*1)组、突变杂合子(*1/*1G)组、突变纯合子(* 1G/* 1G)组的羟氯喹血药浓度分别为(807.2±455.9),(705.4±331.9)和(229.5±89.8)ng·mL-1,依次降低.GG组和GA组较AA组的羟氯喹血药浓度差异均有统计学意义(均P＜0.05).ABCG2基因的野生纯合子(GG)组、突变杂合子(GT)组和突变纯合子(rr)组的羟氯喹血药浓度分别为(732.2±424.4),(764.5 ±371.9)和(271.0±148.5)ng·mL-1,各基因型组之间的羟氯喹血药浓度差异均无统计学意义(均P＞0.05).结论 CYP3A4* 1G等位基因突变可使羟氯喹血药浓度降低,而ABCG2等位基因突变对羟氯喹的血药浓度无明显影响.“,”Objective To study the correlation between cytochrome P (CYP) 450 3A4 and ATP-binding cassette sub-family G member 2 (ABCG2) genotypes and the concentration of hydroxychloroquine (HCQ) in systemic lupus erythematosus (SLE) patients.Methods Forty-six SLE were recruited and their blood HCQ concentrations were determined.The CYP3A4 * 1G (rs2242480) and ABCG2 (rs2231142) genotypes were analyzed by Sanger sequencing.The influences of these genotypes on the concentrations of HCQ were studied.Results The blood concentrations of patients with CYP3A4 * 1 G wild-type homozygous (* 1/* 1),heterozygous mutant (* 1/* 1G) and homozygous mutant (*1G/*1G) were (807.2±455.9),(705.4±331.9) and (229.5 ± 89.8) ng · mL-1.And the blood concentrations of GG,GT and TT genotypes of ABCG2 were (732.2 ±424.4),(764.5 ±371.9),(271.0 ±148.5) ng · mL-1.No significant difference could be shown in patients with ABCG2 genotypes (P ＞ 0.05).Conclusion In SLE therapy,patients with CYP3A4 * 1G gene exhibit lower blood concentrations than the non-carriers.The single nucleotide polymorphisms (SNPs)ABCG2 do not affect the blood concentration and efficacy of HCQ.