抗结核急性药物性肝损伤患者GCLM、GCLC和GSTP1基因多态性的关系

摘要/Abstract

摘要： 目的分析谷氨酰半胱氨酸连接酶修饰亚基(GCLM)与催化亚基(GCLC)、谷胱甘肽S转移酶P1(GSTP1)基因多态性与抗结核急性药物性肝损伤(AADLI)的关系。方法选取92例抗结核急性药物性肝损伤患者为研究组,未出现抗结核急性药物性肝损伤患者86例为对照组。采用聚合酶链反应限制性片段长度多态法(PCR-RFLP)检测GCLM基因T-588C位点、GCLC基因C-129T位点、GSTP1基因Ile105Val位点多态性。Hardy-weinberg遗传平衡定律验证各基因型频率是否具有代表性,采用Logistic法对影响AADLI发生的相关因素进行分析。结果 GCLM基因T-588C、GCLC基因C-129T、GSTP1基因Ile105Val位点存在单核苷酸多态性,各基因型频率稳定且符合Hardy-Weinberg遗传平衡定律;两组间GCLM T-588C位点TT、GCLC C-129T位点CC与GSTP1 Ile105Val位点GG基因型分布比较差异有统计学意义(P<0.05)。Logistic分析显示GCLM T-588C位点TT、GCLC C-129T位点CC、GSTP1 Ile105Val位点GG基因型均为AADLI发生的危险因素。结论 GCLM T-588C、GCLC C-129T、GSTP1 Ile105Val基因多态性与AADLI发病有关,各基因位点TT、CC、GG基因型可增加IPAH的发病风险。

关键词: 谷氨酰半胱氨酸连接酶, 谷胱甘肽S转移酶P1, 抗结核急性药物性肝损伤

Abstract: Objective To analyze the relationship of polymorphisms of glutamate cysteine ligase modifier (GCLM) subunit, glutamate cysteine ligase catalytic (GCLC) subunit and glutathione S transferase P1 (GSTP1) with acute anti-tuberculosis drug-induced liver injury (AADILI).Methods In our study, 92 cases with AADILI were enrolled as the study group and 86 cases without AADILI were enrolled as the control group. T-588C loci of GCLM gene, C-129T loci of GCLC gene and Ile105Val loci of GSTP1 gene were detected using polymerase chain reaction restriction fragment length polymorphism. Representativeness of genotype frequencies were verified using Hardy-Weinberg equilibrium. Factors related to the occurrence of AADILI were analyzed using Logistic method.Results There were single nucleotide polymorphisms (SNPs) at T-588C loci of GCLM gene, C-129T loci of GCLC gene and Ile105Val loci of GSTP1 gene, which were stable and in accordance with Hardy-Weinberg equilibrium. There were significant differences in genotype distributions of TT at GCLM T-588C loci, CC at GCLC C-129T loci and GG at GSTP1 Ile105Val loci between the 2 groups (P< 0.05). Genotypes of TT at GCLM T-588C loci, CC at GCLC C-129T loci and GG at GSTP1 Ile105Val loci were risk factors for AADILI.Conclusion The SNPs of GCLM T-588C, GCLC C-129T and GSTP1 Ile105Val genes are associated with AADILI susceptibility. TT at GCLM T-588C loci, CC at GCLC C-129T loci and GG at GSTP1 Ile105Val loci can increase the risk of AADILI.

Key words: Glutamate cysteine ligase, Glutathione S transferase P1, Acute anti-tuberculosis drug-induced liver injury

王赟, 鲍靖. 抗结核急性药物性肝损伤患者GCLM、GCLC和GSTP1基因多态性的关系[J]. 肝脏, 2019, 24(2): 138-142.

WANG Yun, BAO Jing. Relationships of GCLM, GCLC and GSTP1 gene polymorphisms in patients with anti-tuberculosis drug-induced liver injury[J]. Chinese Hepatolgy, 2019, 24(2): 138-142.

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