Centre for Genomics and Personalised Health, Queensland University of Technology, Brisbane, QLD, 4059, Australia.
Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, 4059, Australia.
Pharmacogenomics J. 2022 Mar;22(2):100-108. doi: 10.1038/s41397-021-00262-4. Epub 2021 Nov 25.
Indigenous Australians face a disproportionately severe burden of chronic disease relative to other Australians, with elevated rates of morbidity and mortality. While genomics technologies are slowly gaining momentum in personalised treatments for many, a lack of pharmacogenomic research in Indigenous peoples could delay adoption. Appropriately implementing pharmacogenomics in clinical care necessitates an understanding of the frequencies of pharmacologically relevant genetic variants within Indigenous populations. We analysed whole-genome sequence data from 187 individuals from the Tiwi Islands and characterised the pharmacogenomic landscape of this population. Specifically, we compared variant profiles and allelic distributions of previously described pharmacologically significant genes and variants with other population groups. We identified 22 translationally relevant pharmacogenomic variants and 18 clinically actionable guidelines with implications for drug dosing and treatment of conditions including heart disease, diabetes and cancer. We specifically observed increased poor and intermediate metabolizer phenotypes in the CYP2C9 (PM:19%, IM:44%) and CYP2C19 (PM:18%, IM:44%) genes.
澳大利亚原住民患慢性病的负担比其他澳大利亚人不成比例地严重，发病率和死亡率都更高。虽然基因组学技术在许多疾病的个体化治疗方面正在缓慢取得进展，但原住民人群中缺乏药物基因组学研究可能会延迟其应用。要在临床护理中适当实施药物基因组学，就需要了解在原住民群体中与药理学相关的遗传变异的频率。我们分析了来自 Tiwi 群岛的 187 个人的全基因组序列数据，并对该人群的药物基因组学图谱进行了描述。具体来说，我们比较了先前描述的具有重要药理学意义的基因和变异在该人群中的变体图谱和等位基因分布情况，并与其他人群进行了比较。我们确定了 22 个具有转化意义的药物基因组学变异和 18 个具有临床意义的指南，这些指南对药物剂量和包括心脏病、糖尿病和癌症在内的疾病的治疗都有影响。我们特别观察到 CYP2C9（PM：19%，IM：44%）和 CYP2C19（PM：18%，IM：44%）基因中不良和中间代谢物表型的增加。
