Division of Anatomical Pathology, Faculty of Health Sciences, University of Stellenbosch, PO Box 19063, Tygerberg 7505, South Africa.
Metab Brain Dis. 2012 Sep;27(3):255-66. doi: 10.1007/s11011-012-9296-8. Epub 2012 Apr 19.
Chronic, multi-factorial conditions caused by a complex interaction between genetic and environmental risk factors frequently share common disease mechanisms, as evidenced by an overlap between genetic risk factors for cardiovascular disease (CVD) and Alzheimer's disease (AD). Single nucleotide polymorphisms (SNPs) in several genes including ApoE, MTHFR, HFE and FTO are known to increase the risk of both conditions. The E4 allele of the ApoE polymorphism is the most extensively studied risk factor for AD and increases the risk of coronary heart disease by approximately 40%. It furthermore displays differential therapeutic responses with use of cholesterol-lowering statins and acetylcholinesterase inhibitors, which may also be due to variation in the CYP2D6 gene in some patients. Disease expression may be triggered by gene-environment interaction causing conversion of minor metabolic abnormalities into major brain disease due to cumulative risk. A growing body of evidence supports the assessment and treatment of CVD risk factors in midlife as a preventable cause of cognitive decline, morbidity and mortality in old age. In this review, the concept of pathology supported genetic testing (PSGT) for CVD is described in this context. PSGT combines DNA testing with biochemical measurements to determine gene expression and to monitor response to treatment. The aim is to diagnose treatable disease subtypes of complex disorders, facilitate prevention of cumulative risk and formulate intervention strategies guided from the genetic background. CVD provides a model to address the lifestyle link in most chronic diseases with a genetic component. Similar preventative measures would apply for optimisation of heart and brain health.
慢性、多因素疾病是由遗传和环境风险因素之间复杂相互作用引起的，通常具有共同的疾病机制，这一点可以从心血管疾病 (CVD) 和阿尔茨海默病 (AD) 的遗传风险因素之间的重叠得到证明。几种基因中的单核苷酸多态性 (SNP)，包括 ApoE、MTHFR、HFE 和 FTO，已知会增加这两种疾病的风险。ApoE 多态性的 E4 等位基因是 AD 最广泛研究的风险因素，使冠心病的风险增加约 40%。此外，它还显示出使用降胆固醇他汀类药物和乙酰胆碱酯酶抑制剂的治疗反应存在差异，这也可能是由于一些患者中 CYP2D6 基因的变异。疾病的表现可能是由基因-环境相互作用引发的，导致轻微的代谢异常转化为主要的大脑疾病，因为累积的风险。越来越多的证据支持在中年期评估和治疗 CVD 风险因素，因为这是导致老年认知能力下降、发病率和死亡率的可预防原因。在这篇综述中，描述了这种情况下 CVD 的病理支持性基因检测 (PSGT) 的概念。PSGT 将 DNA 测试与生化测量相结合，以确定基因表达并监测治疗反应。其目的是诊断可治疗的复杂疾病亚型，促进累积风险的预防，并根据遗传背景制定干预策略。CVD 为解决大多数具有遗传成分的慢性疾病中的生活方式联系提供了一个模型。类似的预防措施将适用于优化心脏和大脑健康。
