MnSOD的基因多态性与抗结核药物性肝损害关系的研究

The relationship between the polymorphism of MnSOD gene and antituberculosis drug-induced liver injury

目的研究药物代谢酶锰超氧化物歧化酶(MnSOD)的基因多态性与抗结核药物肝损害的关系,阐明抗结核药物诱导肝损害的分子机制。方法通过聚合酶链反应-直接测序(PCR-DS)方法分析101例有抗结核药物性肝损害的结核病患者(病例组)及107例无抗结核药物性肝损害的结核病患者(对照组)的MnSOD的基因多态性,并分析它们与抗结核药物性肝损害之间的关系。结果与MnSOD编码基因47位碱基T/T基因型(OR:0.68,P>0.05)、T/C基因型(OR:1.03,P>0.05)比较,47位碱基C/C基因型患者更易发生抗结核药物性肝损害,OR值为5.77(P<0.05)。结论 MnSOD编码基因的47位碱基CC基因型有可能是发生抗结核药物性肝损害的易感基因。

Objective To study the relationship between the gene polymorphism of drug metabolizing emzyme MnSOD and antituberculosis drug-induced liver injury. Methods The genes coding MnSOD from 101 tuberculosis （TB） cases with antituberculosis drug-induced liver injury and 107 TB cases without antituberculosis drug-induced liver injury were amplified and sequenced. Their genotypes were determined and the genotype frequencies were compared between cases and controls using SPSS12.0 software. The relationship between gene polymorphisms and antituberculosis drug-induced liver injury was analyzed. Results The base C/C at position 47 （47C/C） of MnSOD gene （OR： 5.77, P〈0.05） had significantly higher risk of antituberculosis drug-induced liver injury than 47T/T （OR： 0.68, P〉0.05） and 47T/C （OR： 1.03, P〉0.05）. Conclusion The 47C/C of MnSOD were significantly associated with a higher risk of developing antituberculosis drug-induced liver injury.