The role of NAT2 polymorphism and methylation in anti-tuberculosis drug-induced liver injury in Mongolian tuberculosis patients.

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 non-parametric 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 patients. With the increase of the total methylation level of NAT2 gene promoter region, the risk of ATLI increased gradually. (OR = 8.371, 95% CI: 2.391 ~ 29.315). CpG1, CpG4, CpG9, CpG10 and CpG11.12 were positively correlated with a total methylation level in the ATLI group. WHAT IS NEW AND CONCLUSION: The detection rate of ATLI in Mongolian tuberculosis patients was 27.6%, and there were differences in the NAT2 genotypes and acetylated phenotypes. The slow acetylated type was the risk factor for ATLI. Methylation in the promoter region of the NAT2 gene has an effect on the risk of ATLI. After adjusting for the interference of three acetylation types, it was found that the total methylation of the promoter region of NAT2 gene in Mongolian tuberculosis patients is an independent influencing factor of ATLI. Furthermore, there is a moderate to high correlation between some sites and the overall level of methylation.

Effect of soybean protein on blood pressure in postmenopausal women: a meta-analysis of randomized controlled trials.

The effect of soybean protein on blood pressure (BP) in postmenopausal women is controversial, so we aimed to conduct a systematic review and a meta-analysis of published randomized controlled trials (RCTs) to investigate whether supplementation with soy protein improves their blood pressure. PubMed and Embase were searched up to February 2016. Weighted mean differences were calculated for net changes in BP by using fixed-effect or random-effect models. Subgroup and meta-regression analyses were performed to clarify heterogeneity among the trials. A total of twelve trials (1551 postmenopausal women participants) were included in the present meta-analysis. The overall pooled estimates of the effect of soy protein indicated a significant effect on systolic blood pressure (SBP) (mean difference: -3.03 mmHg; 95% CI: -5.03, -1.02; P = 0.003) and diastolic blood pressure (DBP) (mean difference: -0.71 mmHg; 95% CI: -1.26, -0.16; P = 0.012). Subgroup analyses further demonstrated that soy protein intake ≥25 g d-1 significantly reduced BP, and the mean difference in SBP and DBP was -4.62 mmHg (95% CI: -8.42, -0.81; P = 0.04) and -1.63 mmHg (95% CI: -2.85, -0.41; P = 0.009), respectively. Soy isoflavone intake ≥100 mg d-1 had a better reduction effect both in SBP (-5.47 mmHg; 95% CI: -8.42, -2.51; P = 0.00) and DBP (-2.03 mmHg; 95% CI: -3.35, -0.72; P = 0.002). However, soy protein intake <25 g d-1 or soy isoflavone intake <100 mg d-1 had no such effects (P > 0.05). This meta-analysis suggests that ingestion of ≥25 g soy protein per day has BP-lowering effects, and the improvements in BP may be due to the isoflavones component of soy protein. More high-quality RCTs need to be carried out to confirm the present findings.