纤维细胞生长因子1基因和高血压:从定量特征位置到位置分析
Maciej Tomaszewski1, Fadi J Charchar, Mark D Lynch
1British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK. mt142@le.ac.uk
Circulation
|October 3, 2007
概括
纤维细胞生长因子1基因 (FGF1) 的遗传变异与高血压有关. 在高血压患者中,脏FGF1表达的增加表明FGF1在血压调节中的作用.
科学领域:
- 遗传学 是一个遗传学.
- 心血管疾病 心血管疾病
- 分子生物学分子生物学
背景情况:
- 染色体5的长臂与高血压有关,并含有调节血压的基因.
- 以前的研究将这种染色体区域与高血压联系起来.
研究的目的:
- 识别与高血压相关的特定基因和遗传变异.
- 研究纤维细胞生长因子1 (FGF1) 在血压调节中的作用.
主要方法:
- 微卫星标记物的精细映射和使用单核酸多态 (SNP) 的链接不平衡映射.
- 基于家族的关联分析和定量聚合酶连锁反应 (qPCR) 以及用于基因表达分析的西式涂抹.
- 脏免疫组织化学测试以确定FGF1局部.
主要成果:
- 联系分析证实了5号染色体区域与血压的关联 (Z=3.51,P=0.0002).
- 纤维细胞生长因子1 (FGF1) 被确定为一个定位候选基因.
- 在FGF1的基因变异,特别是内部SNPrs152524的基因变异,与高血压显著相关 (P=0.0026).
- 与正常血压对照组相比,高血压患者显示脏FGF1mRNA和蛋白质表达增加.
- FGF1的表达局限于脏中的质内皮细胞和中细胞.
结论:
- 在FGF1内的遗传变异与家族血压升高有关.
- 脏FGF1表达的升调可能会调解FGF1和高血压之间的关联.
- 为了验证这些发现,需要在不同的队列中进行进一步的复制.
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