Vasto Sonya, Candore Giuseppina, Duro Giovanni, Lio Domenico, Grimaldi Maria Paola, Caruso Calogero
Università di Palermo, Gruppo di Studio sull'Immunosenescenza, Dipartimento di Biopatologia e Metodologia Biomediche, Corso Tukory 211, 90134 Palermo, Italy.
Pharmacogenomics. 2007 Dec;8(12):1735-45. doi: 10.2217/14622416.8.12.1735.
Inflammation plays a key role in Alzheimer disease, and dissecting the genetics of inflammation may provide an answer to the possible treatment. The next-generation therapy is based on a pharmacogenomics that will reconure new approaches to a drug used on definite people with specific dosage. The translation of pharmacogenomics into clinical practice will allow bold steps to be taken toward personalized medicine. In response to tissue injury elicited by trauma or infection, the inflammatory response sets in as a complex network of molecular and cellular interactions, directed to facilitate a return to physiological homeostasis and tissue repair. The role of an individual's genetic background and predisposition for the extent of an inflammatory response is determined by variability of genes encoding endogenous mediators that constitute the pathways of inflammation. Due to its clinical relevance, in this review, the view on genetics of inflammation will be illustrated through a description of the genetic basis of a specific inflammatory disease, Alzheimer's disease (AD). Several studies report a significantly different distribution, in patients and controls, of proinflammatory genes, alleles of which are under-represented in control subjects and over-represented in patients affected by AD. These studies will permit the detection of a risk profile that will potentially allow both the early identification of individuals susceptible to disease and the possible design or utilization of drug at the right dose for a desired effect - a pharmacogenomic approach for this disease.
炎症在阿尔茨海默病中起关键作用，剖析炎症的遗传学特征可能为潜在的治疗方法提供答案。下一代疗法基于药物基因组学，它将为特定人群确定特定剂量的用药提供新方法。将药物基因组学转化为临床实践将朝着个性化医疗迈出大胆的步伐。针对由创伤或感染引发的组织损伤，炎症反应作为一个复杂的分子和细胞相互作用网络启动，旨在促进恢复生理稳态和组织修复。个体的遗传背景和炎症反应程度的易感性由编码构成炎症途径的内源性介质的基因变异性决定。鉴于其临床相关性，在本综述中，将通过描述一种特定炎症性疾病——阿尔茨海默病（AD）的遗传基础，来说明对炎症遗传学的观点。多项研究报告称，促炎基因在患者和对照组中的分布存在显著差异，其等位基因在对照受试者中代表性不足，而在AD患者中代表性过高。这些研究将有助于检测出一种风险特征，这可能使我们既能早期识别易患该病的个体，又能针对预期效果以正确剂量设计或使用药物——针对这种疾病的药物基因组学方法。
