人类UDP-glycosyltransferase基因家族的人口规模变异性
Daianna González-Padilla1, Mahamadou D Camara2, Volker M Lauschke3
1Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Journal of genetics and genomics = Yi chuan xue bao
|July 5, 2024
概括
人类的UDP-葡萄糖转移酶 (UGTs) 是药物代谢的关键酶. 这项研究全面描述了UGT遗传变异性,确定了许多罕见和有害的变异,影响药物反应和癌症风险.
科学领域:
- 药物基因组学和人类遗传学
- 酶学和药物代谢 药物代谢
背景情况:
- 人类UDP-葡萄糖转移酶 (UGTs) 催化了内源性化合物和异生菌的糖化,影响了药物的疗效和毒性.
- UGT基因的遗传变异有助于药物反应和疾病易感性的个体间变异性,但缺乏全面的遗传分析.
研究的目的:
- 对人类UGT基因家族的遗传变异性进行全面评估.
- 通过使用新型预测算法,识别和功能解释UGT基因内的误解变异.
主要方法:
- 利用了来自7个主要人类群体的141,456名个体的全外体和全基因组测序数据.
- 开发并应用了基因家族特定的变异效应预测器,以评估UGT误解变异的功能影响.
- 进行结构分析以证实基质结合部位上预测的变异效应.
主要成果:
- 在UGT基因家族中发现了9666种外来变异,其中98.9%被归类为罕见.
- 预测1,208种有害的UGT变种,主要在非洲和南亚人群中观察到.
- 结构分析证实了UGT基质结合位点内的几个变体的功能影响.
结论:
- 提供了人类UGT基因家族遗传变异性的系统概述.
- 突出了已识别的有害变种在解释2期新陈代谢中个体间差异的潜力.
- 便于将基因测序数据转化为UGT基质配置和临床结果的个性化预测.
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