RESUMO
Antituberculosis drug-induced liver injury (ATDILI) is a common side effect leading to tuberculosis (TB) treatment disruption. The mechanism of the disease remains poorly understood. We conducted a genomewide association study (GWAS) to investigate all possible genetic factors of ATDILI in Thai patients. This study was carried out in Thai TB patients, including 79 ATDILI cases and 239 tolerant controls from our network hospitals in Thailand. Nearly 1 million single-nucleotide polymorphisms (SNPs) were genotyped across the whole genome using an Illumina OmniExpress Exome BeadChip array. In the discovery stage, we identified strong association signals on chromosome 8 originating from the N-acetyltransferase (NAT2) region. The A allele of rs1495741, the top SNP in the intergenic region of NAT2 and PSD3 (14 kb from NAT2), was significantly associated with ATDILI (recessive model, odds ratio of 6.01 [95% confidence interval, 3.42 to 10.57]; P = 6.86E-11). This particular SNP was reported as a tag SNP for NAT2 inferred phenotypes. The AA, AG, and GG genotypes represented NAT2 slow acetylators, intermediate acetylators, and fast acetylators, respectively. The tag SNP genotypes demonstrated a concordance rate of 94.98% with NAT2 acetylator phenotypes. This GWAS shows that NAT2 is the most important risk factor for ATDILI in the Thai population.
Assuntos
Antituberculosos/efeitos adversos , Arilamina N-Acetiltransferase/genética , Estudo de Associação Genômica Ampla/métodos , Polimorfismo de Nucleotídeo Único/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença Hepática Induzida por Substâncias e Drogas/genética , Feminino , Predisposição Genética para Doença/genética , Genótipo , Haplótipos/genética , Humanos , Masculino , Pessoa de Meia-Idade , TailândiaRESUMO
Background: Medication non-adherence in tuberculosis (TB) patients is an obstacle to TB treatment. Directly observed treatment to monitor and ensure adherence still has some limitations in high TB-burden countries. Most digital adherence technologies emphasize medication-taking reminder functions; however, a bi-directional communication platform to provide patient-health workers with an interface that focuses on enhancing medication adherence is likely to improve medical adherence. A budgeted mobile-based system called CARE-call providing both functions was developed and evaluated concerning whether it could enhance medication adherence.Design: Mixed methods combined quantitative and qualitative approaches. One hundred TB patients were randomized into intervention or control groups. Medication adherence rates between the two groups were compared. A focus group discussion was conducted to obtain in-depth perspectives from the patients.Results: At a 90% adherence level, the number of non-adherence patients in the intervention group was significantly lower than that of the control group (7.5% vs. 27.5%, p= .037). The participants were satisfied with the functions provided by the system, especially the confidentiality of the monitoring process, which did not involve monitoring by imaging or video recording. The bi-directional communication enabled them to contact health staff when concerns arose during the treatment course. Poor mobile phone signals and fast battery drain were reported as major technical problems of the system.Conclusions: The CARE-call system was able to prevent non-adherence in this rural setting in Thailand. However, further investigation with a larger sample size should be conducted on whether the system can also improve successful TB treatment outcome.