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目的探讨汉族人群N-乙酰基转移酶2(NAT2)基因多态性与抗结核药物性肝损害(ATDLI)易感性的关系。方法回顾性分析抗结核治疗后发生肝损害的结核病患者228例(肝损害组),未发生肝损害的结核病患者260例(无肝损害组),应用时间飞行质谱技术(MassARRAY)检测NAT2基因多态性。结果在筛选出的10个标签单核苷酸多态性(tagSNP)位点中,NAT2启动子区域rs4646243的T等位基因和rs4646246的A等位基因构成的突变纯合及杂合基因型均与抗结核药物性肝损害保护性有关联,rs1115784、rs1041983和rs1799930的纯合突变基因型与抗结核药物性肝损害风险相关联,其中rs1041983和rs1799930的突变纯合基因型与抗结核药物性肝损害高度关联。在10个标签SNP位点中发现2个单体域,位于单体域1的单体型‘TGAA’和位于单体域2的单体型‘TAG’与抗结核药物性肝损害相关联。在NAT2基因上还发现2个抗结核药物性肝损害保护性的单体型:位于单体域1的单体型‘CGGG’及位于单体域2的‘CGG’。结论汉族人群NAT2基因多态性与抗结核药物性肝损害的发生密切相关,通过检测NAT2基因及单体型,可以在抗结核治疗前筛选出肝损害发生风险较高的患者。
Objective To investigate the relationship between polymorphism of N-acetyltransferase 2 (NAT2) gene and the susceptibility to anti-TB drug-induced liver injury (ATDLI) in Han population. Methods A total of 228 tuberculosis patients with liver damage (liver damage group) and 260 tuberculosis patients without liver damage (without liver damage group) were retrospectively analyzed. Mass NATR gene was detected by Mass-flow cytometry State. Results In the ten tag SNP loci, both the homozygous and heterozygous genotypes of the T allele of rs4646243 and the A allele of rs4646246 in the NAT2 promoter region And anti-TB drug-induced liver injury protection is associated with rs1115784, rs1041983 and rs1799930 homozygous mutant genotype and anti-TB drug-induced liver injury risk associated with rs1041983 and rs1799930 mutant homozygous genotype and anti-TB drug-induced liver Damage is highly correlated. Two haplotypes were found in ten SNP sites, haplotype TGAA located in monomeric domain 1 and haplotype TAG located in monomeric domain 2 were associated with anti-TB drug-induced liver damage. Two anti-tuberculosis drug-induced liver damage protective haplotypes were also found on the NAT2 gene: haplotype CGGG in monomeric domain 1 and CGG in monomeric domain 2. Conclusion NAT2 gene polymorphism in Han population is closely related to the occurrence of anti-TB drug-induced liver damage. By detecting NAT2 gene and haplotype, the patients with high risk of liver damage can be screened before antituberculosis treatment.