Franks P W
Genetic Epidemiology & Clinical Research Group, Department of Public Health & Clinical Medicine, Section for Medicine, Umeå University Hospital, Umeå, Sweden.
J Hum Hypertens. 2009 Apr;23(4):227-37. doi: 10.1038/jhh.2008.134. Epub 2008 Nov 13.
Hypertension segregates within families, indicating that genetic factors explain some of the variance in the risk of developing the disease; however, even with major advances in genotyping technologies facilitating the discovery of multiple genetic risk markers for cardiovascular and metabolic diseases, little progress has been made in defining the genetic defects that cause elevations in blood pressure. Several plausible explanations exist for this apparent paradox, one of which is that the risk conveyed by genes involved in the development of hypertension is context dependent. This notion is supported by a growing number of published animal and human studies, although none has yet provided unequivocal evidence that genetic and environmental factors interact to influence the risk of primary hypertension in humans. In this review, an assumption is made that common genetic variation contributes meaningfully to the development of primary hypertension. The review focuses on (i) several methodological limitations of genetic association studies and (ii) the roles that gene-environment interactions might play in the development of primary hypertension. The proceeding sections of the review examine the design features necessary for future studies to adequately test the hypothesis that genes for primary hypertension act in a context-dependent manner. Finally, an outline of how knowledge of gene-environment interactions might be used to optimize the prevention or treatment of primary hypertension is provided.
高血压在家族中具有聚集性，这表明遗传因素可解释部分疾病发生风险的差异；然而，尽管基因分型技术取得了重大进展，有助于发现心血管和代谢疾病的多种遗传风险标记，但在确定导致血压升高的遗传缺陷方面进展甚微。对于这一明显的矛盾现象，存在几种合理的解释，其中之一是，参与高血压发生的基因所传递的风险取决于具体情况。越来越多已发表的动物和人体研究支持了这一观点，尽管尚无研究能提供明确证据表明遗传和环境因素相互作用会影响人类原发性高血压的风险。在本综述中，我们假定常见的基因变异对原发性高血压的发生有重要影响。本综述重点关注：（i）遗传关联研究的若干方法学局限性；（ii）基因-环境相互作用在原发性高血压发生过程中可能发挥的作用。本综述接下来的部分将探讨未来研究为充分验证原发性高血压相关基因以取决于具体情况的方式发挥作用这一假说所需的设计特点。最后，概述了如何利用基因-环境相互作用的知识来优化原发性高血压的预防或治疗。
