The genetic response to short-term interventions affecting cardiovascular function: Rationale and design of the Heredity and Phenotype Intervention (HAPI) Heart Study
The genetic response to short-term interventions affecting cardiovascular function: Rationale and design of the Heredity and Phenotype Intervention (HAPI) Heart Study
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DOI：
10.1016/j.ahj.2008.01.019
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发表时间：
2008-05-01
影响因子：
4.8
通讯作者：
Shuldiner, Alan R.
中科院分区：
文献类型：
--
作者：
Mitchell, Braxton D.;McArdle, Patrick F.;Shuldiner, Alan R.
背景心血管疾病(CVD)的病因是多因素的。到目前为止，识别影响心血管疾病风险的基因的努力取得的成果有限，这可能是因为常见的心血管疾病风险等位基因的效应量较小，以及存在基因和环境的相互作用。方法Hapi心脏研究始于2002年，旨在评估4种影响心血管风险因素的短期干预措施对心血管的反应，并确定这些反应的遗传和环境决定因素。测量包括对冷加压负荷试验和高盐饮食的血压反应，对高脂肪挑战的甘油三酯漂移，对阿司匹林治疗的血小板聚集反应。结果干预措施在868名来自大家庭的相对健康的阿米什成年人中进行。每个干预的反应性状的遗传度在8%到38%之间，这表明与每个干预的反应相关的一些变异可以归因于基因的相加效应。结论识别这些反应基因可能会识别影响心血管疾病的新机制，并可能导致个体化的预防策略和提高对高危个体的早期发现。
Background The etiology of cardiovascular disease (CVD) is multifactorial. Efforts to identify genes influencing CVD risk have met with limited success to date, likely because of the small effect sizes of common CVD risk alleles and the presence of gene by gene and gene by environment interactions.Methods The HAPI Heart Study was initiated in 2002 to measure the cardiovascular response to 4 short-term interventions affecting cardiovascular risk factors and to identify the genetic and environmental determinants of these responses. The measurements included blood pressure responses to the cold pressor stress test and to a high salt diet, triglyceride excursion in response to a high-fat challenge, and response in platelet aggregation to aspirin therapy.Results The interventions were carried out in 868 relatively healthy Amish adults from large families. The heritabilities of selected response traits for each intervention ranged from 8% to 38%, suggesting that some of the variation associated with response to each intervention can be attributed to the additive effects of genes.Conclusions Identifying these response genes may identify new mechanisms influencing CVD and may lead to individualized preventive strategies and improved early detection of high-risk individuals.