抗结核治疗肝损害患者NAT2、Mn SOD的基因多态性研究

doi:10.3969/j.issn.1006-3110.2017.07.016

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摘要目的探讨抗结核治疗肝损害患者N-乙酰基转移酶2(NAT2)、锰超氧化物歧化酶(Mn SOD)的基因多态性,探讨NAT2、Mn SOD的基因多态性与肝损害之间的分子机制,为肝损害的防治提供参考。方法选取新乡医学院第一附属医院2015年1-12月期间诊断为肺结核行抗结核治疗的133例患者,采用聚合酶链反应检测患者NAT2、Mn SOD的基因多态性,分析结果。结果患者发生肝损害者46例,发生率为34.59%;患者NAT2等位基因型共检出6种,分别为NAT2*4、NAT2*6、NAT2*7、NAT2*5B、NAT2*5C、NAT2*5A,出现频率分别为50.75%、24.06%、16.17%、4.89%、2.26%、1.88%。27例患者为快乙酰化基因型、71例为中乙酰化基因型、35例为慢乙酰化基因型,分别占20.30%、53.38%、26.32%。有肝损害患者中20例(43.48%)为慢乙酰化基因型、26例(56.52%)为中、快乙酰化基因型,无肝损害患者中15例(17.34%)为慢乙酰化基因型、72例(82.76%)为中、快乙酰化基因型,两者比较差异有统计学意义(χ²=10.68,P<0.05);患者Mn SOD基因在47位碱基上存在单核苷酸多态性,84例患者为T/T基因型、37例为T/C基因型、12例为C/C基因型,分别占63.16%、27.82%、9.02%。有肝损害患者中23例(50.00%)为T/T、10例(21.74%)为T/C、13例(28.26%)为C/C,无肝损害患者中58例(66.67%)为T/T、22例(25.29%)为T/C、7例(8.05%)为C/C,有肝损害患者中C/C基因型比例明显高于无肝损害患者,差异有统计学意义(χ²=9.62,P<0.05)。结论抗结核治疗肝损害患者NAT2慢乙酰化基因型及Mn SOD基因47位C/C基因明显升高,可能参与了患者肝损害的发生。

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	刘卫国
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关键词 ：抗结核, 肝损害, NAT2, MnSOD, 基因多态性

Abstract：Objective To explore the genetic polymorphisms of drug metabolizing enzymes N-acetyltransferase (NAT2)and Mn-superoxide dismutase (Mn-SOD) in patients with anti-tuberculosis drug-induced liver injury, and to study the association of NAT2 and Mn-SOD genetic polymorphisms with molecular mechanisms of liver injury so as to provide references for prevention and treatment of liver damage. Methods We collected 133 patients diagnosed as tuberculosis (TB) and treated with anti-tuberculosis drugs in the First Affiliated Hospital of Xinxiang Medical College from January to December in 2015. The genetic polymorphisms of NAT2 and Mn-SOD were determined using polymerase chain reaction, and then the results were analyzed. Results Forty-six patients had liver damage, with the incidence rate of 34.59%. 6 NAT2 genotypes, including NAT2*4, NAT2*6, NAT2*7, NAT2*5B, NAT2*5C and NAT2*5A, were detected in the 133 patients, and their frequencies were 50.75% 24.06%, 16.17%, 4.89%, 2.26% and 1.88% respectively. 27 (20.30%) patients had fast-acetylator NAT2 genotype, 71 (53.38%) had middle-acetylator NAT2 genotype and 35 (26.32%) had slow-acetylator NAT2 genotype. For patients with liver injury, 20 (43.48%) cases had slow-acetylator NAT2 genotype and 26 (56.52%) had middle- and fast-acetylator NAT2 genotypes, while for the patients without liver injury, 15 (17.34%) had slow-acetylator NAT2 genotype and 72 (82.76%) had middle- and fast-acetylator NAT2 genotypes , showing statistically significant difference (χ²=10.68, P<0.05). Single nucleotide polymorphisms were found in 47 loci of Mn-SOD gene in the 133 patients, and 84 (63.16%) had T/T genotype, 37 (27.82%) had T/C genotype and 12 (9.02%) had C/C genotype. For the patients with liver injury, 23 (50.00%) had T/T genotype, 10 (21.74%) had T/C genotype and 13 (28.26%) had C/C genotype, while for the patients without liver injury, 58 (66.67%) had T/T genotype, 22 (25.29%) had T/C genotype and 7 (8.05%) had C/C genotype , indicating statistically significant difference (χ²=9.62, P<0.05). Conclusions The slow-acetylator genotype of NAT2 and Mn-SOD 47C/C genotype in the patients with anti-tuberculosis drug-induced liver injury are significantly increased, which may be involved in the pathogenesis of liver injury.

Key words： anti-tuberculosis liver injury NAT2 Mn SOD gene polymorphism

收稿日期: 2016-12-10

R521

作者简介: 刘卫国(1968-),男,河南延津人,学士,副主任医师,研究方向:结核病诊治。

引用本文:

刘卫国, 崔俊伟, 李振云, 王永亮, 马军珂. 抗结核治疗肝损害患者NAT2、Mn SOD的基因多态性研究[J]. 实用预防医学, 2017, 24(7): 823-826. LIU Wei-guo, CUI Jun-wei, LI Zhen-yun, WANG Yong-liang, MA Jun-ke. Genetic polymorphisms of NAT2 and Mn-SOD in patientswith anti-tuberculosis drug-induced liver injury. , 2017, 24(7): 823-826.

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