Posthuma Danielle, Meulenbelt Ingrid, de Craen Anton J M, de Geus Eco J C, Slagboom P Eline, Boomsma Dorret I, Westendorp Rudi G J
Department of Biological Psychology, Vrije Universiteit Amsterdam, the Netherlands.
Twin Res Hum Genet. 2005 Apr;8(2):132-7. doi: 10.1375/1832427053738728.
Through its ability to induce the enhanced release and production of cytokines, amyloid-beta is responsible for the chronic inflammatory response that contributes to Alzheimer's disease (AD). Determining whether the response of monocytes to amyloid-beta stimulation is under genetic control may help understand the basis of why some people are more prone to develop neuronal degeneration than others. In the current study we investigated the heritability of the cytokine (IL-10, IL-6, IL-1beta, IL-1ra, TNF-alpha) production capacity upon ex vivo stimulation with amyloid-beta in whole blood samples of 222 twins and 85 singleton siblings from 139 extended twin families. It was found that individual differences in amyloid-beta induced cytokine production capacity are to a large extent of genetic origin, with heritability estimates ranging from 55% (IL-1beta) to 68% (IL-6). We conclude that genes influencing amyloid-beta-induced cytokine response may provide clues to the progression of AD pathology.
β-淀粉样蛋白能够诱导细胞因子的释放和产生增强，从而引发导致阿尔茨海默病（AD）的慢性炎症反应。确定单核细胞对β-淀粉样蛋白刺激的反应是否受基因控制，可能有助于理解为何有些人比其他人更容易发生神经元退化的原因。在本研究中，我们调查了来自139个扩展双胞胎家庭的222对双胞胎和85名单胎兄弟姐妹的全血样本在体外用β-淀粉样蛋白刺激后细胞因子（IL-10、IL-6、IL-1β、IL-1ra、TNF-α）产生能力的遗传性。结果发现，β-淀粉样蛋白诱导的细胞因子产生能力的个体差异在很大程度上源于基因，遗传率估计范围为55%（IL-1β）至68%（IL-6）。我们得出结论，影响β-淀粉样蛋白诱导的细胞因子反应的基因可能为AD病理学进展提供线索。
