缺氧反应有助于改变基因表达和状细胞疾病患者的毛囊前肺高血压
Xu Zhang1, Wei Zhang, Shwu-Fan Ma
1Comprehensive Sickle Cell Center, Section of Hematology/Oncology (X.Z., S.S., V.R.G.), Section of Cardiology (A.A.D.), and Section of Pulmonary, Critical Care, and Sleep Medicine (J.G.N.G., R.F.M.), Department of Medicine, Institute of Human Genetics (W.Z., R.K.), Department of Pediatrics (W.Z.), and Institute for Personalized Respiratory Medicine (A.A.D., T.A., N.G.C., J.G.N.G., R.F.M.), University of Illinois at Chicago, Chicago, IL; Section of Pulmonary/Critical Care, Department of Medicine, University of Chicago, Chicago, IL (S-F.M.); Chuvash Republic Clinical Hospital 2, Cheboksary, Russia (G.M.); Cheboksary Children's Hospital, Cheboksary, Russia (A.S.); Center for Sickle Cell Disease, Howard University, Washington, DC (T.A., M.X., S.N.); Department of Medicine, Boston University School of Medicine, Boston, MA (M.H.S., C.T.B.); Department of Biostatistics, Boston University School of Public Health, Boston, MA (P.S.); Hematology Division, University of Utah, Salt Lake City, UT (J.T.P.).
在状细胞疾病 (SCD) 中,缺氧反应会影响基因表达和肺高血压. 一种特定的基因变异 (rs10857560) 与这种严重并发症的风险增加有关.
科学领域:
- 遗传学 是一个遗传学.
- 分子生物学分子生物学
- 心血管医学 心血管医学
背景情况:
- 状细胞疾病 (SCD) 与肺高血压有关,这是一种与死亡率相关的并发症.
- 假定缺氧反应会改变SCD中的基因表达,导致疾病并发症.
研究的目的:
- 为了识别SCD中低氧反应调节的基因,与贫血效应不同.
- 在SCD患者中调查基因表达变异与毛囊前肺高血压之间的关联.
主要方法:
- 从SCD患者和楚瓦什多细胞血症患者的外周血液单核细胞中比较基因表达.
- 利用关联映射来识别SCD患者中缺氧反应基因的表达定量特征位点 (eQTL).
- 在两个独立的SCD队列中验证了MAPK8eQTL (rs10857560) 与毛囊前肺高血压的关联.
主要成果:
- 在SCD和楚瓦什多细胞瘤中确定了1040个基因的变异表达,包括MAPK8.8.
- 在SCD患者中发现了103个低氧反应基因,具有显著的eQTL.
- 一个MAPK8eQTL的rs10857560的A等位基因与757名SCD患者的毛囊前肺高血压有很强的关联,具有与减少MAPK8表达相关的同卵性AA基因型.
结论:
- 这项研究证实了SCD.中显著的缺氧转录成分.
- 一个特定的MAPK8表达定量特征位点 (rs10857560) 与状细胞疾病中的毛囊前肺高血压有关.
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