摘要
目的分析OATP1B1和CYP3A5*3基因多态性与抗结核药物性肝损伤的关系。方法采用病例对照研究设计,随机选取抗结核治疗致肝损伤的患者160例为病例组,无肝损伤的结核患者145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OATP1B1-388A>G位点及CYP3A5*3-6986A>G位点多态性;利用SPSS21.0软件对基因型分布进行χ2检验,并进行多因素logistics回归分析。结果病例组和对照组比较性别、吸烟者比例差异无统计学意义(P>0.05);饮酒者比例两组间比较差异有统计学意义(OATP1B1-388A>G,χ2=6.900,P<0.01;CYP3A5*3-6986A>G,χ~2=8.322,P<0.01),即与肝损伤具有相关性;OATP1B1-388A>G位点及CYP3A5*3-6986A>G位点的各基因型在两组中的分布差异均有统计学意义(P<0.01),其突变频率分别为70.82%和70.16%。多因素logistics回归分析调整饮酒因素后,OATP1B1-388A>G位点及CYP3A5*3-6986A>G位点的突变型(AG、GG)仍为ADLI的危险因素,但二者在抗结核药致肝损伤的过程中无交互作用。结论OATP1B1-388A>G位点及CYP3A5*3-6986A>G位点的多态性与ADLI的发生具有相关性,其中突变型可使ADLI发生风险增加。
Objective To examine the relationship between polymorphisms of the organic anion transporting polypeptide(OATP1 B1)gene and the cytochrome P450 3 A5*3(CYP3 A5*3)gene and anti-tuberculosis drug-induced liver injury(ADLI). Methods A case-control study was conducted.One hundred and sixty patients with tuberculosis and ADLI served as cases,and 145 patients with tuberculosis without liver injury served as controls.Polymerase chain reactionrestriction fragment length polymorphism(PCR-RFLP)was used to identify the genotypes of the OATP1 B1-388 A>G gene and the CYP3 A5*3-6986 A>G gene.Data on genotype distribution was analyzed using the software SPSS 21.0,and multi-factor regression analysis was performed using logistic regression. Results Gender and smoking did not differ in cases and controls(P>0.05);Alcohol consumption differed significantly in the two groups(OATP1 B1-388 A>G,χ~2=6.900,P<0.01,CYP3 A5*3-6986 A>G,χ2=8.322,P<0.01),which indicated that alcohol consumption was associated with liver injury.The frequency of AA and AG/GG in OATP1 B1-388 A>G was respectively 21.88%and 78.12%in cases and 37.24% and 62.76%in controls,while the frequency of AA and AG/GG in CYP3 A5*3-6986 A>G was18.12%and 81.88%in cases and 42.76% and 57.24%in controls.Results indicated that the frequency of both mutations differed significantly in the two groups(P<0.01).The frequency of a mutation was respectively 70.82% and 70.16%in the two groups.After adjusting for alcohol consumption as a factor in multi-factor regression analysis,mutations(AG and GG)in OATP1B1(388 A>G)and CYP3 A5*3(6986 A>G)were still risk factors for ADLI.However,the two mutations did not interact in liver injury induced by antituberculosis drugs. Conclusion The OATP1 B1-388 A>G and CYP3 A5*3-6986 A>G polymorphisms were correlated with ADLI,and those mutations were deemed to be risk factors for ADLI.
作者
廖彥
林翀
林明冠
钟业腾
陈少文
苏应仙
何晶
LIAO Yan;LIN Chong;LIN Ming-guan;ZHONG Ye-teng;CHEN Shao-wen;SU Ying-xian;HE Jing(Clinical Laboratory,The Second Hospital Affiliated with Hainan Medical University,Haikou,China570311;Infectious Diseases,The Second Hospital Affiliated with Hainan Medical University)
出处
《中国病原生物学杂志》
CSCD
北大核心
2019年第1期106-109,共4页
Journal of Pathogen Biology
基金
海南省卫生厅医学科研立项课题项目(琼卫2014-自筹50号)
作者简介
通讯作者:林翀,E-mail:lybt.com@163.com;廖彥(1971-),女,副主任技师,主要从事临床生化,临检及临床微生物检验工作。E-mail:ly65399014@163.com
