在台湾汉族人口中对HLA区域的现象景观和药物遗传学影响
Wan-Hsuan Chou1, Lu-Chun Chen1, Henry Sung-Ching Wong1
1Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan.
Biomarker research
|May 3, 2024
概括
一个新的参考小组准确地归因于台湾个体的人类白细胞抗原 (HLA) 变异. 这项研究描述了HLA遗传和表型格局,并量化了与药物不良反应相关的HLA等位基因患病率.
科学领域:
- 基因组学和人类遗传学
- 药物基因组学 药物基因组学
- 人口遗传学 人口遗传学
背景情况:
- 人类白细胞抗原 (HLA) 基因非常多样化,影响疾病易感性和药物反应.
- 高的HLA测序成本和特定种群的遗传结构需要定制的归算面板.
- 了解台湾人口中的HLA变异是有限的.
研究的目的:
- 开发一个台湾特定的HLA归算参考小组.
- 描述台湾HLA变异的遗传和表型格局.
- 为了估计与药物不良反应 (ADR) 相关的HLA等位基因的患病率.
主要方法:
- 使用845名台湾受试者的基因型和HLA测序数据创建和训练了归算模型.
- 在59,448名受试者中应用HLA归算,以确定等位基因和单位基因的频率.
- 进行了一项全现象关联研究 (PheWAS),并分析了HLA氨基酸多态性和ADR相关的等位基因.
主要成果:
- 参考小组实现了高准确度 (98.9-99.3%) 的HLA等位基因归算.
- 确定了HLA变体和26种表型之间的18,136个显著关联,包括与结性脊髓炎和过敏的新型联系.
- 在台湾人群中表征了关键的药物基因学HLA等位基因 (例如,HLA-C*01:02,HLA-B*58:01,HLA-B*15:02) 的流行.
结论:
- 成功地为一个大型台湾队列归因了HLA变异,揭示了遗传和表型景观.
- 量化了与ADR相关的HLA等位基因的流行率,提供了关键的人口特异性数据.
- 开发的参考小组将有助于未来研究HLA变异在台湾人口中的多种表型中的作用.
关键词:
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