染色体5q上的APOO伪基因与低密度脂蛋白胆固醇水平有关
May E Montasser1, Elizabeth A O'Hare1,2, Xiaochun Wang1
1Division of Endocrinology, Diabetes and Nutrition (M.E.M., E.A.O., X.W., A.D.H., R.M., J.A.P., K.A.R., A.R.S., B.D.M., N.A.Z., Y.-P.C.C.), Department of Medicine, University of Maryland School of Medicine, Baltimore.
Circulation
|March 30, 2018
概括
研究人员发现了一种新基因APOOP1,该基因显著增加低密度脂蛋白胆固醇 (LDL-C) 的水平. 这一发现为脂质稳定和心血管疾病风险因素提供了新的理解.
科学领域:
- 遗传学
- 分子生物学
- 心血管研究
背景情况:
- 低密度脂蛋白胆固醇 (LDL- C) 的升高是心血管疾病的主要危险因素.
- 已知的遗传变异只能解释大约20%的LDL-C水平变化.
- 鉴定LDL-C的新遗传贡献者对于理解脂质平衡至关重要.
研究的目的:
- 确定导致LDL-C水平变化的基因.
- 研究一种新发现的基因变异在胆固醇代谢中的作用.
- 阐明一种调节脂质平衡的新机制.
主要方法:
- 在1102名阿米什人中进行了基于阵列的关联分析.
- 基因分析,包括重组映射.
- 斑马鱼模型和体外实验来评估基因功能.
主要成果:
- 在5号染色体上发现了一种与LDL-C增加15mg/dL相关的创始类型.
- 在斑马鱼模型中转录的假基因APOOP1的表达增加了LDL- C和血管斑块的形成.
- 在相关区域内,APOOP1被确定为强有力的候选基因.
结论:
- 建议APOOP1调节人类的LDL- C水平.
- 这一发现揭示了脂质平衡的一个新机制.
- APOOP1 代表了管理心血管疾病风险的潜在新目标.
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