摘要
目的探讨尿营二磷酸葡萄糖醛酸转移酶1A6(UGT1A6)基因多态性与中国唐山地区结核患者抗结核药致肝损害的相关性。方法采用病例对照研究,以抗结核治疗导致肝损害患者202例为病例组,无肝损害者239例为对照组,收集环境因素暴露情况及静脉血。UGT1A6基因多态性分析采用聚合酶链反应限制性片段长度多态方法,利用HhaⅠ、DpnⅡ和NsiⅠ内切酶分析其基因多态性,以SPSS13.0软件对各危险因素进行单因素和多因素非条件Logistic回归分析。结果UGT1A6的19T/G、308C/A和541A/G多态性位点均存在3种基因型,UGT1A619T/T、UGT1A619T/G和UGT1A6—19G/G在病例组和对照组的频率分别为51.5%、39.6%、8.9%和71.1%、25.5%、3.3%;UGT1A6—308C/C、UGT1A6308C/A和UGT1A6—308A/A在病例组和对照组的频率分别为52.0%、40.6%、7.4%和79.1%、19.2%、1.7%;UGT1A6541AA、UGT1A6—541A/G和UGT1A6541G/G在病例组和对照组的频率分别为57.9%、33.7%、8.4%和79.5%、19.2%、1.3%,两组问差异均有统计学意义(x^2值分别为17.956、37.385和24.095,P值均〈0.01)。单因素和多凶素分析均显示UGT1A619T/G、308C/A、541A/G3个位点基因多态性与抗结核药致肝损害的发生有关(P值均〈0.05)。结论UGT1A6基因多态性可能与汉族人抗结核药致肝损害的发病有关,且各基因型存在相互作用。
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 UGT 1A6-19T/G, UGT 1A6-308C/A and UGT 1 A6-541A/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 The allele frequency ofgene UGTIA6-19T/T, UGT1A6-19T/G, UGTIA6-19G/G, GT1A6-308C/ C, UGT1A6-308C/A, UGTI A6-308A/A, UGT1 A6-541AA, 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 〈 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.
出处
《中华肝脏病杂志》
CAS
CSCD
北大核心
2011年第3期201-204,共4页
Chinese Journal of Hepatology
基金
唐山市重点实验室项目(08150201A-1-8)
关键词
结核
肺
抗结核药
尿苷二磷酸葡萄糖醛酸转移酶1A6
多态性
基因
肝损害
Tuberculosis, pulmonary
Antitubercular agents
UDP-glucuronosyltransferase 1A6
Polymorphism, genes
Hepatic injures