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.
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.