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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 investigate the association between gene E308G polymorphism of flavin-containing monooxygenase (FMO3) and liver damage in patients with Graves' disease (GD) in Shandong Province. Methods The subjects were selected from 105 patients with Graves disease (GD group) who were admitted to Department of Endocrinology and Hospitalized from March 2011 to April 2012. The patients were divided into two subgroups: liver methionine group Damage group) and methimazole before and after treatment of normal liver function group (normal liver function group). The clinical data of patients were collected and their peripheral non-anticoagulant venous blood clots were collected and genomic DNA was extracted. The E308G site of flavin monooxygenase 3 gene was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) Genotypes were calculated for genotype and allele frequency in both groups. Results The frequencies of AG + GG genotype and G allele in E308G site of flavin monooxygenase 3 gene were significantly different between liver damage group and normal liver function group (χ2 = 7.744, P = 0.005; χ2 = 4.850, P = 0.028). Logistic regression analysis showed that the G allele of the E308G site of flavin monooxygenase 3 gene was associated with the occurrence of liver damage induced by methimazole with OR of 3.371 and 95% CI of 1.357-8.379 (P <0.05). Conclusion The polymorphism of flavin monooxygenase 3 gene E308G may be associated with methimazole-induced liver damage in GD patients of Han nationality in Shandong province.