Department of Science and Technology/National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research/Medical Research Council Centre for Molecular and Cellular Biology, Division of Molecular Biology and Human Genetics, Faculty of Health Sciences, Stellenbosch University, Cape Town, South Africa.
Int J Tuberc Lung Dis. 2011 Mar;15(3):344-51.
Western Cape and Eastern Cape Provinces, South Africa.
To assess the potential association between the evolution of extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis and mutations in the inhA promoter or the katG gene.
Analysis of the frequency distribution of isoniazid (INH) resistance conferring mutations in a population sample of drug-resistant isolates of M. tuberculosis.
In the Western Cape and Eastern Cape Provinces, the percentage of isolates exhibiting inhA promoter mutations increased significantly from respectively 48.4% and 62.4% in multidrug-resistant tuberculosis (MDR-TB) isolates to 85.5% and 91.9% in XDR isolates. Data from the Western Cape revealed that significantly more XDR-TB isolates showed mutations in the inhA promoter than in katG (85.5% vs. 60.9%, P < 0.01), while the respective proportions were equal for INH-resistant non-MDR-TB isolates (∼30%).
inhA promoter mutations are strongly associated with XDR-TB in South Africa. We suggest that this is due to the dual resistance to ethionamide and (low-dose) INH conferred by inhA promoter mutations. The use of molecular probe assays such as the GenoType® MTBDRplus assay, which allows the detection of inhA promoter mutations, could enable treatment regimens to be adjusted depending on the pharmacogenetic properties of the mutations detected.
南非西开普省和东开普省。
评估广泛耐药（XDR）结核分枝杆菌菌株的进化与异烟肼（INH）耐药相关突变 inhA 启动子或 katG 基因之间的潜在关联。
对耐药结核分枝杆菌分离株人群样本中 INH 耐药相关突变的频率分布进行分析。
在西开普省和东开普省，MDR-TB 分离株 inhA 启动子突变的比例分别从 48.4%和 62.4%显著增加至 XDR 分离株的 85.5%和 91.9%。西开普省的数据显示，XDR-TB 分离株中 inhA 启动子突变的比例明显高于 katG（85.5%比 60.9%，P<0.01），而 INH 耐药非 MDR-TB 分离株的比例相等（约 30%）。
inhA 启动子突变与南非的 XDR-TB 密切相关。我们认为，这是由于 inhA 启动子突变同时赋予了乙硫异烟胺和（低剂量）INH 的双重耐药性。使用分子探针检测，如 GenoType® MTBDRplus 检测，可以根据检测到的突变的遗传药理学特性调整治疗方案。
