Abstract:
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.
journal_name
J Clin Pharm Therjournal_title
Journal of clinical pharmacy and therapeuticsauthors
Zhang D,Hao J,Hou R,Yu Y,Hu B,Wei Ldoi
10.1111/jcpt.13097subject
Has Abstractpub_date
2020-06-01 00:00:00pages
561-569issue
3eissn
0269-4727issn
1365-2710journal_volume
45pub_type
杂志文章abstract:WHAT IS KNOWN AND OBJECTIVE:Low levels of serum triiodothyronine (T3) are a strong predictor of mortality and poor prognosis in critical care patients. Few reports, however, have focused on neurocritical patients. The application of hormone replacement therapy (HRT) in the treatment of neurocritical patients with low T...
journal_title:Journal of clinical pharmacy and therapeutics
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doi:10.1111/jcpt.13162
更新日期:2020-08-01 00:00:00
abstract:WHAT IS KNOWN AND OBJECTIVE:Inhaled treprostinil represents an attractive alternative to the other available prostacyclin formulations by obviating the use of continuous infusions and its associated risks. Published evidence describing the process of transition from infusion prostacyclin therapy to inhaled treprostinil...
journal_title:Journal of clinical pharmacy and therapeutics
pub_type: 杂志文章
doi:10.1111/jcpt.12170
更新日期:2014-10-01 00:00:00
abstract:OBJECTIVE:A population analysis of the kinetics of valproic acid (VPA) in children with epilepsy was performed in order to characterize the covariates which influence VPA clearance (CL). METHODS:A total of 770 steady-state serum concentration samples was analysed. These were collected during VPA therapy from 255 child...
journal_title:Journal of clinical pharmacy and therapeutics
pub_type: 杂志文章
doi:10.1046/j.1365-2710.1999.00202.x
更新日期:1999-02-01 00:00:00
abstract:WHAT IS KNOWN AND OBJECTIVE:Two NS3/4A protease inhibitors (PIs), telaprevir and boceprevir, were recently approved in the United States. The primary objective was to compare the efficacy and safety of triple therapies including either PI to dual therapy in patients with chronic hepatitis C genotype 1; the secondary ob...
journal_title:Journal of clinical pharmacy and therapeutics
pub_type: 杂志文章,meta分析,评审
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更新日期:2014-02-01 00:00:00
abstract:BACKGROUND:Patients' own medications (POM) are medications that patients have obtained in the community setting and bring to the hospital when admitted. The practice of using POMs has not been well studied. OBJECTIVE:To identify benefits, risks and other impacts on the use of POM in hospitals. METHODS:A systematic se...
journal_title:Journal of clinical pharmacy and therapeutics
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2710.2006.00773.x
更新日期:2006-12-01 00:00:00
abstract:WHAT IS KNOWN AND OBJECTIVE:Polypharmacy has a significant impact on patients' health with overall expenditure on over-the-counter (OTC) medicines representing a substantial burden in terms of cost of treatment. The aim of this study, which was conducted within the framework of a European Project funded by the European...
journal_title:Journal of clinical pharmacy and therapeutics
pub_type: 杂志文章,多中心研究
doi:10.1111/jcpt.12601
更新日期:2018-02-01 00:00:00
abstract::The in vitro dissolution rates of 5 and 10 mg nifedipine capsules from eight suppliers were measured in simulated gastric fluid using the rotating paddle apparatus. A total of fourteen products were tested and the performance was found to be satisfactory for all products (> 80% dissolution in 20 min). ...
journal_title:Journal of clinical pharmacy and therapeutics
pub_type: 杂志文章
doi:10.1111/j.1365-2710.1995.tb00656.x
更新日期:1995-08-01 00:00:00
abstract:PURPOSE:To estimate the prevalence of potentially severe drug-drug interactions (DDIs) and their relationship with age, sex and number of prescribed drugs. METHODS:We analysed all prescriptions dispensed from 1 January 2003 to 31 December 2003 to individuals aged 65 or more registered under the Local Health Authority ...
journal_title:Journal of clinical pharmacy and therapeutics
pub_type: 杂志文章
doi:10.1111/j.1365-2710.2009.01021.x
更新日期:2009-08-01 00:00:00
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journal_title:Journal of clinical pharmacy and therapeutics
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doi:10.1111/j.1365-2710.2009.01117.x
更新日期:2010-08-01 00:00:00
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journal_title:Journal of clinical pharmacy and therapeutics
pub_type: 杂志文章,随机对照试验
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pub_type: 杂志文章
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journal_title:Journal of clinical pharmacy and therapeutics
pub_type: 杂志文章
doi:10.1111/j.1365-2710.2007.00894.x
更新日期:2008-04-01 00:00:00
abstract:OBJECTIVE:To evaluate the usefulness of intervention in drug interactions of antiretroviral drugs with coadministered agents by a clinical pharmacist in outpatient HIV-treatment. METHODS:The study design included two intervention arms (A and B), which were both preceded by a control observation period. In arm A, a com...
journal_title:Journal of clinical pharmacy and therapeutics
pub_type: 杂志文章
doi:10.1111/j.1365-2710.2003.00541.x
更新日期:2004-04-01 00:00:00
abstract:OBJECTIVE:There is a growing interest in investigating the role of glutamate receptors in the pathophysiology of schizophrenia. Indeed, the hyperdopaminergic theory of schizophrenia can explain only the positive symptoms of schizophrenia, whereas the glutamate hypothesis may provide a more comprehensive view of the ill...
journal_title:Journal of clinical pharmacy and therapeutics
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1046/j.1365-2710.1999.00238.x
更新日期:1999-10-01 00:00:00
abstract::Blood ribavirin concentration was monitored after the administration of high-dose oral ribavirin in a case of adenovirus-induced haemorrhagic cystitis post-stem-cell transplantation. Combination use of intravenous gamma immunoglobulin (15 g/3 days) and high-dose ribavirin (RBV; 9000 mg/4 days) provided plasma ribaviri...
journal_title:Journal of clinical pharmacy and therapeutics
pub_type: 杂志文章
doi:10.1111/j.1365-2710.2008.00874.x
更新日期:2008-02-01 00:00:00
abstract:WHAT IS KNOWN AND OBJECTIVE:The pharmacokinetic-pharmacodynamic parameter that best predicts the efficacy of vancomycin is the ratio of the area under the concentration versus time curve (AUC) to the minimum inhibitory concentration (MIC). A 24-h AUC (AUC24 )/MIC ratio ≥ 400 was recommended in an American consensus rev...
journal_title:Journal of clinical pharmacy and therapeutics
pub_type: 杂志文章
doi:10.1111/jcpt.12399
更新日期:2016-08-01 00:00:00
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journal_title:Journal of clinical pharmacy and therapeutics
pub_type: 杂志文章
doi:10.1111/jcpt.12474
更新日期:2017-02-01 00:00:00
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journal_title:Journal of clinical pharmacy and therapeutics
pub_type: 杂志文章
doi:10.1111/j.1365-2710.1990.tb00407.x
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journal_title:Journal of clinical pharmacy and therapeutics
pub_type: 杂志文章
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更新日期:2014-08-01 00:00:00
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journal_title:Journal of clinical pharmacy and therapeutics
pub_type: 杂志文章
doi:10.1111/j.1365-2710.2009.01037.x
更新日期:2009-10-01 00:00:00
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journal_title:Journal of clinical pharmacy and therapeutics
pub_type: 杂志文章,评审
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更新日期:1993-08-01 00:00:00
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journal_title:Journal of clinical pharmacy and therapeutics
pub_type: 杂志文章,meta分析,评审
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更新日期:2014-06-01 00:00:00
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journal_title:Journal of clinical pharmacy and therapeutics
pub_type: 临床试验,杂志文章
doi:10.1046/j.1365-2710.1998.00132.x
更新日期:1998-02-01 00:00:00
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journal_title:Journal of clinical pharmacy and therapeutics
pub_type: 杂志文章,评审
doi:10.1046/j.1365-2710.2003.00487.x
更新日期:2003-06-01 00:00:00
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journal_title:Journal of clinical pharmacy and therapeutics
pub_type:
doi:10.1111/jcpt.13069
更新日期:2020-04-01 00:00:00
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journal_title:Journal of clinical pharmacy and therapeutics
pub_type:
doi:10.1111/jcpt.13063
更新日期:2020-04-01 00:00:00
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journal_title:Journal of clinical pharmacy and therapeutics
pub_type: 杂志文章
doi:10.1111/jcpt.12257
更新日期:2015-06-01 00:00:00
abstract::The treatment of home-based cancer patients with continuous infusion chemotherapy requires that complete courses of medication in pre-filled syringes are provided on an out-patient basis. The infusion must remain stable prior to use during refrigerated storage (up to 14 days) and during infusion from holster-worn ambu...
journal_title:Journal of clinical pharmacy and therapeutics
pub_type: 杂志文章
doi:10.1111/j.1365-2710.1988.tb00185.x
更新日期:1988-06-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:To assess the accuracy and precision of delivery from containers containing oral drops, both under optimal laboratory conditions and during use by volunteers using a variety of real pharmaceutical products and specially prepared fluids. METHODS:The effects of the physical properties (viscosit...
journal_title:Journal of clinical pharmacy and therapeutics
pub_type: 杂志文章
doi:10.1111/j.1365-2710.2004.00595.x
更新日期:2004-12-01 00:00:00
abstract::A study was conducted in two groups of healthy volunteers to assess whether the time of administration (10 min before the meal versus 60 min after the meal) influences the pharmacokinetics and absorption kinetics of a slow-release theophylline product (Teonova). In the first group (Group A, n = 10), the drug was given...
journal_title:Journal of clinical pharmacy and therapeutics
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1365-2710.1988.tb00509.x
更新日期:1988-02-01 00:00:00