一种HTRA1基因变异增加了与年龄相关的黄斑变性敏感性
Zhenglin Yang1, Nicola J Camp, Hui Sun
1Department of Ophthalmology and Visual Sciences, Moran Eye Center, University of Utah School of Medicine, Salt Lake City, UT 84132, USA.
Science (New York, N.Y.)
|October 21, 2006
概括
研究人员确定了HTRA1基因中的特定基因变异rs11200638作为与年龄相关的黄斑变性 (AMD) 的主要遗传风险因素. 这一发现突显了HTRA1的存在.
科学领域:
- 眼科医生 眼科 眼科
- 遗传学 是一个遗传学.
- 分子生物学分子生物学
背景情况:
- 与年龄相关的黄斑变性 (AMD) 是不可逆转的视力丧失的主要原因.
- 晚年老化表现出显著的遗传成分,在染色体10q26.6上有一个已知的风险位.
- 在10q26时负责AMD风险的特定基因仍未确定.
研究的目的:
- 在10q26位置确定与AMD风险相关的因果基因.
- 调查特定遗传变异在AMD病变发生中的作用.
- 探索AMD患者候选基因的表达和定位.
主要方法:
- 在高加索队列中对581例AMD病例和309例对照进行基因定型.
- 单核酸多态性 (SNP) 分析侧重于10q26区域.
- 在患者样本中对HTRA1mRNA和蛋白质表达的定量分析.
- 使用HTRA1抗体对德鲁森进行免疫组织化学染色.
主要成果:
- 在HTRA1基因的促进体中,特定的SNP,rs11200638,被确定为AMD最可能的因果变异.
- 这种变异为AMD提供了49.3%的大量人口可归因风险.
- 在携带风险等位基因的AMD患者中观察到HTRA1mRNA和蛋白质水平升高.
- 在AMD眼睛中的德鲁森显示HTRA1.1的强烈免疫标记.
结论:
- 在AMD易感性方面,HTRA1基因起着至关重要的作用.
- 在HTRA1中rs11200638变异与AMD风险增加密切相关.
- HTRA1代表了与年龄相关的黄斑变性病变的潜在新途径.
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