肺结核抗结核药物致肝损伤患者HMGB1基因多态性

目的探讨肺结核抗结核药物致肝损伤患者HMGB1基因多态性。方法选择2016年8月-2019年8月中南大学湘雅医院附属海口医院滨江分院收治的肺结核患者200例,发展成ATDH的患者纳入ATDH组(n=79),未发展成ATDH的患者纳入非ATDH组(n=121),检测HMGB1基因单核苷酸多态性(SNPs)位点多态性,采用Logistic回归分析HMGB1多态性位点与ATDH的关系。结果ATDH组HMGB1基因rs1045411位点GG、GA、AA基因型分布频率和G、A等位基因频率与非ATDH组比较,差异有统计学意义(P<0.05),rs1412125、rs1360485以及rs2249825位点基因型分布和等位基因频率与非ATDH组比较,均无统计学差异;在共显性、显性、隐性模式下,ATDH组HMGB1基因rs1045411位点基因型分布与非ATDH组比较,差异有统计学意义(P<0.05),与GG基因型比较,GA和AA基因型与肺结核易感性有关,在超显性模式下,ATDH组HMGB1基因rs1045411位点基因型分布与非ATDH组比较,无统计学差异,而在超显性、共显性、显性以及隐性模式下,rs1412125、rs1360485以及rs2249825位点基因型分布与非ATDH组比较,均无统计学差异;rs1045411位点基因多态性与ATDH的发生存在相关性,且突变型诱发ATDH可能性更大,而rs1412125、rs1360485、rs2249825位点基因多态性与ATDH发生风险无关。结论HMGB1基因为ATDH的易感基因,其rs1045411位点多态性与ATDH的发生密切相关,其中突变型发生ATDH风险升高。

HMGB1 gene polymorphism of patients with liver injury induced by anti-tuberculosis drugs

OBJECTIVE To analyze the high mobility group protein 1(HMGB1)gene polymorphism of the patients with liver injury induced byanti-tuberculosis drugs.METHODS A total of 200 patients with pulmonary tuberculosis who were treated in Binjiang Branch of Haikou Hospital Affiliated to Xiangya Medical College of Central South University from Aug 2016 to Aug 2019 were enrolled in the study,the patients who developed to ATDH were assigned as the ATDH group(n=79),the patients who did not developed to ATDH were set as the non-ATDH group(n=121).The single nucleotide polymorphisms(SNPs)of HMGB1 gene was detected,and Logistic regression analysis was performed for the relationship between the HMGB1 gene polymorphism and the ATDH.RESULTS There were significant differences in the distribution frequencies of GG genotype,GA genotype and AA genotype and frequencies of G allele and A allele at rs1045411 locus of HMGB1 gene between the ATDH group and the non-ATDH group(P<0.05).There were no significant differences in the genotype distribution frequency and allele frequency at rs1412125,rs1360485 and rs2249825 loci between the ATDH group and the non-ATDH group.There was significant difference in the genotype distribution at rs1045411 locus of HMGB1 gene under co-dominant,dominant and recessive modes between the ATDH group and the non-ATDH group(P<0.05).Compared with GG genotype,the GA and AA genotypes were related to the susceptibility to pulmonary tuberculosis.There was no significantly difference in the genotype distribution at rs1045411 locus of HMGB1 gene under the superdominant mode between the ATDH group and the non-ATDH group.There were no significant differences in the genotype distributions at rs1412125,rs1360485 and rs2249825 loci under the superdominant,codominant,dominant and recessive modes between the ATDH group and the non-ATDH group.The rs1045411 locus gene polymorphism was related to the occurrence of ATDH,and the mutant type had greater possibility in inducing ATDH,and gene polymorphisms of rs1412125,rs1360485 and rs2249825 loci had nothing to do with the risk of ATDH.CONCLUSION HMGB1 gene is a susceptibility gene for ATDH,and its rs1045411 locus polymorphism is closely related to the occurrence of ATDH,and the risk of ATDH in mutants is increased.