NAT2 genetic polymorphisms and anti-tuberculosis drug-induced hepatotoxicity in Chinese community population
NAT2 genetic polymorphisms and anti-tuberculosis drug-induced hepatotoxicity in Chinese community population
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中国社区人群NAT2基因多态性与抗结核药物肝毒性
DOI：
10.1016/s1665-2681(19)31446-2
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发表时间：
2012-09-01
影响因子：
3.8
通讯作者：
Zhan, Siyan
中科院分区：
文献类型：
--
作者：
Lv, Xiaozhen;Tang, Shaowen;Zhan, Siyan
背景资料。抗结核药物肝毒性是抗结核治疗过程中最常见、最严重的药物不良反应之一。一些研究人员建议，N-乙酰转移酶2(NAT2)基因的检测可能有助于临床识别高危患者。瞄准。目的：探讨在中国社区结核病人群中，Nat2基因是否可以作为预测急性呼吸窘迫综合征的指标。材料和方法。总共对4304名社区结核病患者进行了6至9个月的前瞻性随访。设计嵌套式病例对照研究。每例患者与对照组按年龄(5岁以内)、性别、治疗史、病情严重程度和用药剂量1：4配对。采用聚合酶链式反应-限制性片段长度多态技术检测NAT2基因的多态性。采用条件Logistic回归模型计算优势比(OR)和95%可信区间(CI)，并计算相应的P值。结果。本研究共纳入89例ATDH患者和356例对照。病例组和对照组等位基因频率分别为4.5%和3.2%，25.3%和26.5%，13.5%和13.5%。病例组和对照组的NAT2*5、NAT2*6和NAT2*7基因频率和等位基因频率差异无统计学意义。中速和慢速乙酰化与快速乙酰化的OR值分别为1.040(95%CI 0.616~1.758)和0.990(95%CI 0.509~1.925)。病例组的Nat2单倍型分布与对照组相似。结论。综上所述，我们在中国社区人群中未发现NAT2基因与ATDH之间存在显著的相关性。在中国社区结核病患者中，以Nat2基因作为ATDH的预测因子可能存在不足。
Background. Anti-tuberculosis drug-induced hepatotoxicity (ATDH) is one of the most prevalent and serious adverse drug reactions in the course of anti-tuberculosis (TB) treatment. Some researchers suggested that determination of N-acetyltransferase 2 (NAT2) genotype may be clinically useful to identify patients at high risk of developing ATDH. Aim. To evaluate whether the NAT2 genotype could be as a predictor for ATDH in Chinese community TB population. Material and methods. A total of 4304 community-based TB patients were followed up six to nine months prospectively. A nested case-control study was designed. Each ATDH case was 1:4 matched with controls by age (within 5 years old), gender, treatment history, disease severity and drug dosage. The polymorphisms of NAT2 were determined using polymerase chain reaction with restriction fragment length polymorphism. Conditional Logistic regression model was used to calculate odds ratio (OR) and 95% confidence interval (CI), as well as corresponding P-values. Results. A total of 89 ATDH cases and 356 controls were included in this study. Allele frequency of NAT2*5, NAT2*6 and NAT2*7 in cases and controls were 4.5 and 3.2%, 25.3 and 26.5%, and 13.5 and 13.5%, respectively. Frequencies of genotypes and alleles of NAT2*5, NAT2*6 and NAT2*7 did not differ significantly between cases and controls. The OR of intermediate acetylator and slow acetylator compared with rapid acetylator was 1.040 (95%CI 0.616-1.758) and 0.990 (95%CI 0.509-1.925), respectively. The NAT2 haplotype distribution in cases was similar to controls. Conclusions. In conclusion, we did not find significant association between NAT2 genotype and ATDH in community-based Chinese population. It may be deficient to take NAT2 genotype as a predictor for ATDH in Chinese community TB patients.