醛脱氢酶基因多态性与系统性红斑狼疮患者环磷酰胺不良反应的相关性  

Relationship between aldehyde dehydrogenase polymorphisms and cyclophosphamide-induced adverse effects in patients with systemic lupus erythematosus

作　　者：陈玲燕[1] 王雪丁[1] 李嘉丽[1] 梁柳琴[2] 辛爽[1] 李宏亮[1] 黄民[1] 

机构地区：[1]中山大学,药学院,广州510080 [2]中山大学附属第一医院,风湿内科,广州510080

出　　处：《中国临床药理学杂志》2014年第3期163-166,共4页The Chinese Journal of Clinical Pharmacology

基　　金：十二五国家科技重大专项基金资助项目(2012ZX09506001-004);国家自然科学基金资助项目(81072708,81173131,81102515)

摘　　要：目的 考察醛脱氢酶（ALDH）的单核苷酸多态性（SNP）与系统性红斑狼疮（SLE）患者用环磷酰胺（CTX）后的不良反应之间的相关性.方法 共纳入93例用CTX的SLE患者,收集全血提取DNA,用DNA阵列质谱基因分型法对ALDH（ALDH1A1 rs6151031,ALDH2 rs671,ALDH3A1 rs2228100）进行基因分型;并分析上述基因型与CTX不良反应的相关性.结果相同剂量下,ALDH3A1 rs2228100突变纯合子（GG）患者用CTX后出现肝功能异常的风险显著高于CC/GC患者（P〈0.001,OR=20.59,95%CI：2.26 187.96）.结论 ALDH3A1 rs2228100突变与CTX肝毒性密切相关.Objective To investigate the relationship between aldehyde dehydrogenase （ALDH） polymorphisms and cyclophosphamide（CTX）-induced adverse effects in patients with systemic lupus erythematosus （SLE）. Methods Blood samples and clinical data were collected from a cohort of 93 unrelated Chinese SLE patients who received cyclophosphamide therapy. ALDH （ALDH1A1 rs6151031, ALDH2 rs671,ALDH3A1 rs2228100） genotypes were detected by MALDI-TOF mass spectrometry. The associations between polymorphisms of ALDH and cyclophosphamide-induced adverse effects were analyzed by Chi-square test. Results ALDH3A1 rs2228100 GG genotype was correlated with an increased risk of abnormal liver function in SLE patients with the same dose of CTX （P〈0.001, OR=20.59, 95%CI：2.26-187.96）. Conclusion ALDH3A1 rs2228100 mutant plays an important role in the incidence of hepatotoxicity, therefore genotyping of ALDH3A1 rs2228100 will be useful in the individualization of CTX therapy in SLE patients.

关 键 词：醛脱氢酶 基因多态性 系统性红斑狼疮 环磷酰胺 

分 类 号：R968[医药卫生—药理学] R979.1[医药卫生—药学]