[Relationship between the polymorphisms of UGT1A6 genes and anti-tuberculosis drug induced hepatic-injury].
[Relationship between the polymorphisms of UGT1A6 genes and anti-tuberculosis drug induced hepatic-injury].
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DOI：
10.3760/cma.j.issn.1007-3418.2011.03.012
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发表时间：
2011-03-01
影响因子：
--
通讯作者：
Feng, Fu-min
中科院分区：
文献类型：
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作者：
Hao, Jin-qi;Chen, Yi;Feng, Fu-min
目的：目的：探讨UGT 1A 6基因多态性与抗结核药物性肝损伤（ADIH）的关系。收集结核病相关危险因素的信息。采用聚合酶链反应-限制性片段长度多态性技术（PCR-RFLP）检测接受抗结核治疗的患者UGT 1A 6 - 19 T/G、UGT 1A 6 - 308 C/A和UGT 1A 6 - 541 A/G基因型。使用Hha I、Dpn II和Nsi I酶。采用SPSS13.0 for windows软件进行单因素和多因素条件Logistic分析。ADIH组UGT 1A 6 - 19 T/T、UGT 1A 6 - 19 T/G、UGT 1A 6 - 19 G/G、GT 1A 6 - 308 C/C、UGT 1A 6 - 308 C/A、UGT 1A 6 - 308 A/A、UGT 1A 6 - 541 AA、UGT 1A 6 - 541 A/G、UGT 1A 6 - 541 G/G等位基因频率为51.5%，对照组分别为39.6%、8.9%、52.0%、40.6%、7.4%、57.9%、33.7%、8.4%和71.1%、25.5%、3.3%、79.1%、19.2%、1.7%、79.5%、19.2%、1.3%。单因素分析显示，病例组UGT 1A 6 - 19 T/G、UGT 1A 6 - 308 C/A和UGT 1A 6 - 541 A/G基因型频率显著高于对照组（P <0.05）。UGT 1A 6突变基因型对肺结核易感性有协同作用。
OBJECTIVE: To investigate the relationship between the polymorphisms of UGT1A6 genes and anti-tuberculosis drug induced hepatic-injury (ADIH).METHODS: 202 cases and 239 controls were collected and a case-control study was conducted. Information on related risk factors of tuberculosis was collected. The genotypes of UGT1A6-19T/G, UGT1A6-308C/A and UGT1A6-541A/G genetic polymorphisms were detected by polymerase chain reaction and restriction fragment length polymorphism technique (PCR-RFLP) in patients received anti-tuberculosis therapy. The Hha I, Dpn II and Nsi I enzyme were employed. Univariate and multivariate conditional logistic analyses were conducted using SPSS13.0 for windows software.RESULTS:RESULTS: The allele frequency of gene UGT1A6-19T/T, UGT1A6-19T/G, UGT1A6-19G/G, GT1A6-308C/C, UGT1A6-308C/A, UGT1A6-308A/A, UGT1A6-541AA, UGT1A6-541A/G and UGT1A6-541G/G in ADIH group were 51.5%, 39.6%, 8.9%, 52.0%, 40.6%, 7.4%, 57.9%, 33.7%, 8.4% and 71.1%, 25.5%, 3.3%, 79.1%, 19.2%, 1.7%, 79.5%, 19.2%, 1.3% in control group, respectively. Univariate analysis demonstrated that the frequency of UGT1A6-19T/G, UGT1A6-308C/A and UGT1A6-541A/G genotype in cases were significantly higher than that in controls (P less than 0.05).CONCLUSION: A positive association is found between UGT1A6 genotype and the occurrence of ADIH. The synergetic effect is proved on susceptibility to pulmonary tuberculosis between UGT1A6 mutant genotypes.