Oelofse Carola, Siwada Anwani, Flisher Khaleila, Möller Marlo, Uren Caitlin
South African Medical Research Council Centre for Tuberculosis Research; Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
Centre for Bioinformatics and Computational Biology, Stellenbosch University, Stellenbosch, South Africa.
Brief Bioinform. 2025 Aug 31;26(5). doi: 10.1093/bib/bbaf484.
Currently, many of the world's most culturally and genetically diverse populations, located in Africa, risk exclusion from advancements in pharmacogenomics (PGx) and personalized medicine. Optimizing treatment outcomes for these populations is crucial, particularly for widespread diseases such as tuberculosis (TB). Reducing adverse drug reactions is essential for improving treatment adherence and overall outcomes. However, investigating the PGx landscape in African populations is challenging due to the lack of genotype and phenotype data, as well as limited computational tools and resources tailored to their genetic diversity. This study assessed various bioinformatic methodologies to characterize variations in the absorption, distribution, metabolism, and excretion (ADME) of anti-TB drugs in a large African cohort (>21 populations from public and in-house datasets). Special focus was placed on the Khoe-San, one of Africa's most genetically diverse groups, and the South African Coloured (SAC) community, whose richly diverse genetic background arises from recent admixture. We developed a graphic resource to support the investigation of anti-TB drug PGx in Africa. African-specific genomic studies addressing major health challenges on the continent are critical for informing the development of relevant genotyping and reference panels, enabling more cost-efficient personalized care in the region. This study offers a comprehensive assessment of the TB PGx landscape in Africa and highlights the potential of computational methods to promote the inclusion of genomically diverse African populations in PGx research.
目前，世界上许多文化和基因高度多样化的人群位于非洲，他们面临着被排除在药物基因组学（PGx）和个性化医疗进展之外的风险。优化这些人群的治疗效果至关重要，尤其是对于结核病（TB）等广泛流行的疾病。减少药物不良反应对于提高治疗依从性和总体治疗效果至关重要。然而，由于缺乏基因型和表型数据，以及针对非洲人群遗传多样性的计算工具和资源有限，在非洲人群中研究PGx情况具有挑战性。本研究评估了各种生物信息学方法，以表征一个大型非洲队列（来自公共和内部数据集的21个以上人群）中抗结核药物吸收、分布、代谢和排泄（ADME）的变异情况。特别关注了非洲遗传多样性最高的群体之一科伊桑人，以及南非混血（SAC）社区，其丰富多样的遗传背景源于近期的基因混合。我们开发了一种图形资源，以支持对非洲抗结核药物PGx的研究。针对非洲大陆主要健康挑战的非洲特异性基因组研究，对于为相关基因分型和参考面板的开发提供信息至关重要，从而能够在该地区实现更具成本效益的个性化医疗。本研究对非洲结核病PGx情况进行了全面评估，并强调了计算方法在促进基因多样化的非洲人群纳入PGx研究方面的潜力。
