What is known and objective: Anti-tuberculosis drug-induced liver injury (ATLI) is one of the most significant adverse reactions for this line of therapy. N-acetyltransferase 2 (NAT2) is an important metabolic enzyme involved in drug metabolism and detoxification. Genetic polymorphism and DNA methylation have been proven to be key factors that affect the expression of NAT2. Therefore, the objective of the study was to investigate the relationship between NAT2 gene polymorphism and DNA methylation in the promoter region with ATLI risk in Mongolian tuberculosis patients. Methods:Our study is a case-control design. Chi-square test, Mann-Whitney U nonparametric test and Pearson test were all used to analyse existing relationships. The association between NAT2 gene acetylation phenotype and the total methylation of the NAT2 promoter region was analysed by means of binary logistic regression analysis. The general situation of the patients was evaluated by questionnaire, and the NAT2 genotyping of the three major polymorphism loci of gene coding was carried out by a gene sequencing technique. The methylation status of the NAT2 gene promoter region was detected by bisulphite sequencing and mass spectrometry.Result and discussion: Our study found that the detection rate of ATLI in Mongolian tuberculosis patients was 27.6%. There were no significant differences in demographic characteristics and living habits amongst the two groups, while significant differences were observed in the polymorphism of the NAT2 genes 481 (rs1799929) and 590 (rs1799930) and the acetylation phenotype. Moreover, the composition and distribution of the NAT2*4/4 and NAT2*4/5 genotypes were found in the two groups. The risk of ATLI in the slow acetylation type was 3.56 times higher than that of the fast acetylation type. Compared with the control group, the CpG5, CpG10, CpG11.12 and total methylation of the NAT2 promoter region in the ATLI group showed a hypermethylated pattern (P < .05). However, on performing binary logistic regression, neither the slow acetylation, intermediate acetylation nor rapid acetylation were found to be associated with ATLI (P > .05). It was found that the total methylation of NAT2 gene promoter region was an independent influencing factor of ATLI in Mongolian tuberculosis How to cite this article: Zhang D, Hao J, Hou R, Yu Y, Hu B, Wei L. The role of NAT2 polymorphism and methylation in anti-tuberculosis drug-induced liver injury in Mongolian tuberculosis patients. J Clin Pharm Ther. 2020;45:561-569.

Background. Side effects of the use of opioid analgesics during painless delivery are the main factors that affect rapid postpartum recovery. Opioid use can result in dangerous respiratory depression in the patient. Opioids can also disrupt the baby’s breathing and heart rate. The nonopioid analgesic dexmedetomidine, a new a2-adrenergic agonist, possesses higher selectivity, greater analgesic effects, and fewer side effects. Moreover, epidural administration of dexmedetomidine also reduces local anesthetic consumption. Objective. Our study aims to compare the analgesic effects as well as the side effects of ropivacaine with dexmedetomidine against sufentanyl as an epidural labor analgesia. Methods. This study is a randomized, double-blinded, controlled trial (registration no. ChiCTR2200055360) involving 120 primiparous (a woman who has given birth once), singleton pregnancy women who are greater than 38 weeks into gestation and have requested epidural labor analgesia. The participants were randomized to receive 0.1% ropivacaine with sufentanyl (0.4 μg/ml) or dexmedetomidine (0.4 μg/ml). The primary outcomes included Visual Analogue Score (VAS), duration of first epidural infusions, the requirement of additional PCEA bolus, and adverse reactions during labor analgesia. Results. Of the 120 subjects who consented, 91 parturient women (women in the condition of labor) had complete data for analysis. Demographics and VAS, as well as maternal and fetal outcomes, were similar between the groups. The duration of first epidural infusions in dexmedetomidine was significantly longer than sufentanyl (median value: 115 vs 68 min, P  < 0.01); the parturient women who received dexmedetomidine and who required additional PCEA bolus were fewer in comparison to those who received sufentanyl (27.5% vs 49.0%, P  < 0.05). Furthermore, the incidence of pruritus in the dexmedetomidine group was lower in comparison to the sufentanyl group (0% vs 11.8%, P  < 0.05). Conclusions. Dexmedetomidine, a nonopioid, is superior to the opioid analgesic sufentanyl in providing a prolonged analgesic effect as an epidural during labor. It also reduces local anesthetic consumption and has fewer side effects. The trial is registered with ChiCTR2200055360.