一个非编码变体的功能机制接近AGTR2与早产风险相关的非编码变体
Li Wang1,2,3,4, Robert M Rossi5,6,7,8, Xiaoting Chen7,9
1Center for Prevention of Preterm Birth, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA. wanglilove2@gmail.com.
BMC medicine
|July 16, 2023
概括
降低了与早产 (PTB) 风险相关的血管新生素II受体2型 (AGTR2) 基因表达,这是由于转录因子在特定遗传位点的结合变化的结果. 增强AGTR2活性可能有助于预防PTB.
科学领域:
- 遗传学和基因组学 遗传学和基因组学
- 生殖生物学 生殖生物学
- 分子生物学分子生物学
背景情况:
- 在37周之前的早产 (PTB) 带来了重大的公共卫生挑战.
- 一项全基因组关联研究确定了与PTB风险相关的血管新生素II受体2型 (AGTR2) 基因附近的非编码基因.
- 在子宫组织中AGTR2表达的降低与增加PTB风险和更短的妊娠期相关.
研究的目的:
- 通过影响转录因子结合,调查确定位置的遗传变异是否会改变AGTR2的表达.
- 为了确定特定的变异及其对AGTR2调节的作用机制.
主要方法:
- 生物信息学分析优先考虑潜在的因果单核酸多态 (SNP).
- 预测基因依赖转录因子 (TF) 的结合.
- 报告员测试以评估变体rs7889204.4的增强剂活性和TF结合影响.
主要成果:
- 变体rs7889204是子宫组织中AGTR2的强表达定量特征位 (eQTL).
- 在rs7889204.4的等位基因之间观察到CCAAT增强剂结合蛋白β (CEBPB) 和homeobox A10 (HOXA10) 的转录因子结合差异.
- rs7889204的风险等位基因"C"显示增强剂活性下降.
结论:
- 由于转录因子结合在rs7889204的受损,AGTR2表达的减少增加了PTB风险.
- 针对AGTR2活动可能是预防PTB的潜在策略.
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