摘要
目的探讨CYP3A5*3和CYP3A4*18B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,发生肝损伤的患者中随机选取175例作为病例组,未发生肝损伤的患者中随机选取185例作为对照组,采用聚合酶链反应-限制性片段长度多态性技术检测研究对象CYP3A5*3、CYP3A4*18B基因多态性。结果 CYP3A5*3-6986A>G位点AA、AG、GG基因型在病例组和对照组频率分别为4.5%、38.9%、56.6%和16.7%、41.1%、42.2%;CYP3A4*18B-20232G>A位点GG、GA、AA基因型在病例组和对照组频率分别为42.3%、46.9%、10.8%和58.9%、34.1%、7.0%,组间差异均有统计学意义(均有P<0.05)。交互作用分析中CYP3A5*3(G)/CYP3A4*18B(G)、CYP3A5*3(G)/CYP3A4*18B(A)分别与CYP3A5*3(A)/CYP3A4*18B(G)比较,差异均有统计学意义(均有P<0.05);CYP3A5*3(A)/CYP3A4*18B(A)与CYP3A5*3(A)/CYP3A4*18B(G)比较,差异无统计学意义(x^2=0.002,P=0.964)。结论 CYP3A5*3及CYP3A4*18B基因多态性与抗结核药物性肝损伤的发生均有关联;CYP3A5*3、CYP3A4*18B两个位点突变可能升高抗结核药物性肝损伤的发生风险,与均不突变相比,CYP3A5*3单一突变也可能升高抗结核药物性肝损伤发生的风险。
Objective To explore the association between the gene polymorphisms of cytochrome CYP3A5 ＊ 3, CYP3A4 ＊ 18B and anti-tuberculosis drug-induced liver injury. Methods A case-control study was conducted. 175 Chi- nese patients with ADLI were selected from the patients who received the anti-tuberculosis therapy as the ADLI group and 185 patients who had not have a hepatic injury were selected as controls. Polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） was used to identify the genotypes of CYP3A5 ＊ 3 gene and CYP3A4 ＊ 18B gene. Re- stilts The frequency of A/G of CYP3A5 ＊ 3-6986 and the frequency of G/A of CYP3A4 ＊ 18B-20232G were 4. 5%, 38. 9% ,56. 6% and 42. 3% ,46.9%, 10. 8% respectively in cases and 16. 7% ,41.1% ,42. 2% and 58. 9%, 34. 1%, 7.0% in controls. There were differences of genetic polymorphisms between CYP3A5 ＊ 3 and CYP3A4 ＊ 18B in the two groups（ all P 〈0. 05 ）. The frequency of the combination of CYP3A5 ＊ 3 （ G）/CYP3A4 ＊ 18B（G） and CYP3A5 ＊ 3 （ G）/ CYP3A4 ＊ 18B（A） between the ease group and the control group had statistically difference（ all P 〈 0. 05 ） when compared with CYP3A5 ＊ 3（A）/CYP3A4 ＊ 18B（G）. The frequency of the combination of CYP3A5 ＊ 3（A）/CYP3A4 ＊ 18B（A）between the ease group and the control group had no statistically difference （ Z2 = 0. 002, P = 0. 964 ） when compared with CYP3 A5 ＊ 3 （A）/CYP3 A4 ＊ 18B （G）. Conclusions The CYP3A5 ＊ 3 and CYP3 A4 ＊ 18 B genetic polymorphisms will raise the risk of liver injury induced by anti-tuberculosis drugs,and the variation combination of CYP3A5 ＊ 3 and CYP3A4 ~ 18B will add to the risk to ADLI. The variation combination of CYP3A5 ＊ 3（ G）/CYP3A4 ＊ 18B（G） will raise the risk of ADLI compared with CYP3A5 ＊ 3 （ A）/CYP3A4 ＊ 18B（G）.
出处
《中华疾病控制杂志》
CAS
CSCD
北大核心
2016年第9期897-900,909,共5页
Chinese Journal of Disease Control & Prevention
基金
唐山市重点实验室基金资助项目(08150201A-1-8)
关键词
抗结核药
肝
多态性
单核苷酸
Anti-tuberculosis drugs
Liver
Polymorphism, single nucleotide
