甲巯咪唑致肝损害与黄素单加氧酶3 E308G位点基因多态性的相关性研究

Relationship between the Flavin-Containing Monooxygenase 3 Gene Polymorphisms and the Liver Injury Caused by Methimazole

目的 探讨黄素单加氧酶3（flavin-containing monooxygenase,FMO3）E308G位点基因多态性与甲巯咪唑（methimazole,MMI）致山东地区汉族Graves病（GD）患者肝损害的相关性。方法 研究对象选自2011年3月至2012年4月到本院内分泌科就诊、住院的Graves病患者（GD组）105例,分为2个亚组：甲巯咪唑治疗后肝损害组（肝损害组）和甲巯咪唑治疗前后肝功正常组（肝功正常组）。记录患者临床资料,收集其外周非抗凝静脉血血凝块,提取基因组DNA,应用聚合酶链反应-限制性片段长度多态性技术（PCR-RFLP）测定黄素单加氧酶3基因E308G位点基因型,计算两组的基因型和等位基因频率。结果 黄素单加氧酶3基因E308G位点的AG＋GG基因型和G等位基因频率在肝损害组与肝功正常组分布差异有统计学意义（χ2=7.744,P=0.005;χ2=4.850,P=0.028）。Logistic回归分析结果显示,黄素单加氧酶3基因E308G位点G等位基因与甲巯咪唑致肝损害的发生相关,OR值为3.371,95%CI为1.357~8.379,P〈0.05。结论 黄素单加氧酶3基因E308G位点多态性可能与山东地区汉族人群GD患者甲巯咪唑致肝损害相关。

OBJECTIVE To explore the relationship between the flavin-containing monooxygenase 3 gene polymorphisms and the liver injury caused by methimazole in the Chinese Han patients with GD in Shandong area. METHODS One hundred and five Patients with GD including 65 patients without liver injury before and after using MMI（ the normal liver function group） and 40 patients with liver injury caused by MMI （the MMI-induced liver injury group）were studied. The genotype and allele frequencies were assayed by polymer- ase chain reaction-restriction fragment length polymorphism （PCR-RFLP）. RESULTS Significant differences in genotype frequencies and allele frequencies were observed in FMO3 E308G between the MMI-induced liver injury group and the normal liver function group（χ2 = 7. 744 ,P = 0. 005 ;χ2 = 4. 850,P = 0. 028 ） . The G allele of FMO3 is associated with the happening of liver injury caused by MMI accord to logistic regression results. CONCLUSION The polymorphism of FMO3 gene might be related to MMI-induced liver injury.