药物基因组学中的祖先多样性影响了西班牙裔/拉丁裔人口的炎症性肠病治疗
Stephanie Ioannou1, Ashley Beecham2, Lissette Gomez2
1Division of Digestive Health and Liver Diseases, University of Miami Miller School of Medicine, Miami, Florida.
概括
由于高白血病风险,在给美洲印第安血统的西班牙裔患者开 thiopurines 之前,对 NUDT15 的基因检测至关重要. rs2097432不是在不同人群中进行HLA-DQA1*05测试的可靠替代品.
科学领域:
- 药物基因组学 药物基因组学
- 胃肠病学 胃肠病学
- 免疫遗传学 免疫遗传学
背景情况:
- 在西班牙裔/拉丁裔社区,炎症性肠病 (IBD) 的患病率正在上升.
- 遗传变异会影响提奥普林和抗TNF治疗的反应.
- 了解不同西班牙裔人口中的药物基因组标记是至关重要的.
研究的目的:
- 在西班牙裔IBD患者中调查遗传多态度 (NUDT15,TPMT,HLA-DQA1*05) 的频率和影响.
- 分析这些变异与硫氨酸诱导的白血病和抗TNF免疫性相关性.
- 评估祖先背景在这些药物基因组学关联中的作用.
主要方法:
- 在2225名西班牙裔参与者中进行了多中心,回顾性队列研究.
- 评估了NUDT15,TPMT和HLA-DQA1*05变异的发生频率.
- 与药物反应,骨髓抑制和抗TNF免疫性相关的遗传变异,考虑到祖先的起源 (欧洲,非洲,美洲印第安人).
主要成果:
- NUDT15和TPMT变种通常很少见,除了美洲印第安人的共同NUDT15变种 (rs116855232).
- NUDT15*4 (rs147390019) 显示,在患有白血病 (23%) 的美洲印第安人中,相对于没有白血病 (3%) 的美国印第安人中,频率明显更高.
- HLA-DQA1*05及其标记rs2097432在祖先之间很常见,并且与抗TNF免疫性有关,但rs2097432只与欧洲祖先的HLA-DQA1*05有关.
结论:
- 在西班牙裔患者与美洲印第安人/阿拉斯加原住民血统治疗前建议进行NUDT15遗传测试.
- rs2097432不应作为不同人群中HLA-DQA1*05测试的替代品.
- 将祖先整合到个性化医疗中对于优化西班牙裔患者IBD治疗至关重要.
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