Multigenerational cohorts in patients with asthma and allergy.
Multigenerational cohorts in patients with asthma and allergy.
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DOI：
10.1016/j.jaci.2016.12.002
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发表时间：
2017-02
期刊：
影响因子：
--
通讯作者：
Holloway JW
中科院分区：
文献类型：
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作者：
Arshad SH;Karmaus W;Zhang H;Holloway JW
最近的观察表明，疾病风险可以跨代传播，而不需要儿童直接暴露于指数环境侮辱，这引发了人们对跨代遗传的兴趣。表观遗传学描述了修饰基因表达而不改变核苷酸序列的过程。表观遗传过程可以在环境暴露的反应中诱导，并可以影响疾病风险，并可能解释这些多代效应。在实验模型中，已经确定了一些表观遗传机制，可以介导表观遗传的垂直传播。然而，这些发现与人类疾病的相关性尚不清楚。另一种模型是疾病风险的跨代遗传需要母亲在怀孕期间存在与妊娠相关的疾病（称为“诱导表观遗传传播模型”）。一些横断面研究调查了过敏和哮喘的多代效应。然而，考虑到哮喘和过敏的早期起源，出生队列研究是研究遗传易感性、表观遗传学和环境暴露影响的理想方法，可以避免回忆偏倚等陷阱，并避免因持续暴露、疾病和治疗而混淆。怀特岛队列的充分表征的三代人包括两个连续的出生队列，提供了可以研究表观遗传信息转移的纵向数据，例如，祖父母吸烟或接触其他有毒化合物的影响。还需要更多的多代出生队列，以确定这一现象的临床相关性，并区分垂直和诱导传播模式，这可能会影响未来的预防战略。
Recent observations that disease risk can be transmitted across generations, without the need for a direct exposure of the child to the index environmental insult, has sparked interest in transgenerational inheritance. Epigenetic describes processes that modify gene expression without a change in the nucleotide sequence. Epigenetic processes can be induced in response to environmental exposures and can influence disease risk, and may explain these multigenerational effects. In experimental models, a number of epigenetic mechanisms have been identified that could mediate vertical transmission of epigenetic inheritance. However, relevance of these findings to human disease is not yet clear. An alternative model is where transgenerational inheritance of disease risk requires the presence of exposure-related diseases in the mother during pregnancy (termed ‘induced epigenetic transmission model’). A number of cross-sectional studies have investigated multigenerational effects in allergy and asthma. However, given early life origins of asthma and allergy, birth cohort studies are ideal to investigate the impact of genetic predisposition, epigenetics, and environmental exposures avoiding pitfalls such as recall bias and confounding by ongoing exposures, disease and treatment. The well characterized, three generations of the Isle of Wight cohort includes two consecutive birth cohorts, providing longitudinal data that can be studied for epigenetic transfer of information, e.g., the effect of grand parental smoking or exposure to other toxic compounds. Further large multigenerational birth cohorts are needed to establish the clinical relevance of this phenomenon and differentiate between vertical and induced transmission models, which may influence future preventive strategies.