硫脲类抗甲亢药物不良反应对比及与HLA-B^(*)38:02:01基因多态性相关性研究

Comparison of Adverse Reactions Between Thioureas Antithyroid Drugs and Their ADR Correlation with HLA-B^(*)38:02:01 Gene Polymorphism

目的探讨HLA-B^(*)38∶02∶01基因多态性与硫脲类抗甲亢药物不良反应的相关性。方法将52例甲状腺功能亢进并行HLA-B^(*)38∶02∶01(rs185386680)基因位点检测的患者作为研究对象,分析比较服用抗甲亢药物(Antithyroid drugs,ATD)丙硫氧嘧啶(PTU)和甲巯咪唑(MMI)后出现皮疹、肝损伤和粒细胞下降不良反应的发生情况,以及对比未出现上述不良反应的患者基因型频率差异。结果服用PTU的患者肝损伤的发生率为39.3%,高于MMI组(8.33%)(P<0.05);而服用MMI的患者粒细胞下降的风险较PTU组更高,差异有统计学意义(P<0.05);同时在粒细胞下降患者中,AG和GG基因型的分布频率较非粒细胞下降患者更高,差异有统计学意义(P<0.01)。结论在甲亢的治疗过程中,不同药物副作用的类型可能不同,PTU易引起肝损伤,而MMI易诱发粒细胞下降,且HLA-B^(*)38∶02∶01(rs185386680)基因突变可能是抗甲亢药物致粒细胞下降的因素之一。

OBJECTIVE To investigate the relationship between the polymorphism of HLA-B^(*)38∶02∶01 gene and the adverse reactions of thiourea antithyroid drugs.METHODS 52 patients with hyperthyroidism who had tested the gene polymorphism HLA-B^(*)38∶02∶01(rs185386680)were included in the study.Adverse drug reactions(ADR)including skin eruption,liver damage and granulocytopenia were compared between methimazole(MMI)treatment patients and propylthiouracil(PTU)treatment patients.And then HLA-B^(*)38∶02∶01 genotype distribution frequency were compared between patients with ADR and those who did not appear ADR.RESULTS The incidence of liver injury in PTU treatment group was 39.3%,which was significantly higher than that in MMI treatment group(8.33%)(P<0.05).The granulocytopenia in patients taking MMI was significantly higher than that in the PTU group(P<0.05).Meanwhile,the distribution frequency of AG and GG genotypes in patients with granulocytopenia were higher than that in patients without granulocytopenia.The difference had statistical significace(P<0.01).CONCLUSION During the treatment of hyperthyroidism,different drugs have different adverse reactions.PTU was easy to cause liver injury,while MMI has more possibility to induce granulocytopenia.And HLA-B^(*)38∶02∶01(rs185386680)gene may be one of the factors causing granulocytopenia by antithyroid drugs.