提丁功能丧失变体与早发性心房之间的关联
Seung Hoan Choi1, Lu-Chen Weng1,2, Carolina Roselli1
1Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, Massachusetts.
JAMA
|December 12, 2018
概括
TTN基因的遗传变异与早发性心房 (AF) 有关. 在早期发作的AF患者中,TTN的功能丧失变异更频繁,这表明存在潜在的遗传联系.
科学领域:
- 遗传学
- 心脏病学
- 基因组学
背景情况:
- 前庭动是一种常见的心律失常,特别是在年轻人中,遗传因素起着重要作用.
- 目前尚不完全了解早期发作的AF的确切遗传机制, 需要进一步研究.
研究的目的:
- 进行大规模的全基因组测序以确定与心房相关的遗传变异.
- 研究功能丧失 (LOF) 变体与早期发作的AF之间的关联.
主要方法:
- 一项病例对照研究利用了Trans-Omics精准医学计划中的18526名个体的全基因组测序数据.
- 与4959名欧洲血统的对照人群进行了比较.
- 结果在英国生物库和MyCode研究中得到验证.
主要成果:
- 在TTN基因中的功能丧失 (LOF) 变异,编码了瘤蛋白质的提丁,在早期发病的AF病例中被发现为2. 1%,而对照组为1. 1% (OR, 1.76).
- TTN LOF变体的存在随着AF发病年龄的提早而增加,特别是在30岁前发病的人群中 (OR,5. 94).
- 这种关联在独立的队列中复制,证实了TTN LOF变体与早期发作的AF之间的联系.
结论:
- 在TTN基因中的功能丧失变异与早期心房之间存在统计学意义上的关联.
- 虽然很少有早期发病的AF病例携带TTN LOF变体,但需要进一步的研究来确定因果关系.
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