Lit Lisa, Enstrom Amanda, Sharp Frank R, Gilbert Donald L
M.I.N.D. Institute, Department of Neurology, University of California at Davis, 2805, 50th Street, Room 2420, Sacramento, CA 95817, United States.
J Psychiatr Res. 2009 Jan;43(3):319-30. doi: 10.1016/j.jpsychires.2008.03.012. Epub 2008 May 15.
Because infection and immune responses have been implicated in the pathogenesis of Tourette syndrome (TS), we hypothesized that children with TS would have altered gene expression in blood compared to controls. In addition, because TS symptoms in childhood vary with age, we tested whether gene expression changes that occur with age in TS differ from normal control children. Whole blood was obtained from 30 children and adolescents with TS and 28 healthy children and adolescents matched for age, race, and gender. Gene expression (RNA) was assessed using whole genome Affymetrix microarrays. Age was analyzed as a continuous covariate and also stratified into three groups: 5-9 (common age for tic onset), 10-12 (when tics often peak), and 13-16 (tics may begin to wane). No global differences were found between TS and controls. However, expression of many genes and multiple pathways differed between TS and controls within each age group (5-9, 10-12, and 13-16), including genes involved in the immune-synapse, and proteasome- and ubiquitin-mediated proteolysis pathways. Notably, across age strata, expression of interferon response, viral processing, natural killer and cytotoxic T-lymphocyte cell genes differed. Our findings suggest age-related interferon, immune and protein degradation gene expression differences between TS and controls.
由于感染和免疫反应与抽动秽语综合征（TS）的发病机制有关，我们推测与对照组相比，TS患儿血液中的基因表达会发生改变。此外，由于儿童期TS症状随年龄变化，我们测试了TS中随年龄发生的基因表达变化是否与正常对照儿童不同。从30名患有TS的儿童和青少年以及28名年龄、种族和性别相匹配的健康儿童和青少年中采集全血。使用全基因组Affymetrix微阵列评估基因表达（RNA）。年龄作为连续协变量进行分析，也分为三组：5 - 9岁（抽动发作的常见年龄）、10 - 12岁（抽动通常达到峰值的年龄）和13 - 16岁（抽动可能开始减弱的年龄）。在TS组和对照组之间未发现总体差异。然而，在每个年龄组（5 - 9岁、10 - 12岁和13 - 16岁）中，TS组和对照组之间许多基因和多个通路的表达存在差异，包括参与免疫突触、蛋白酶体和泛素介导的蛋白水解途径的基因。值得注意的是，在不同年龄层中，干扰素反应、病毒处理、自然杀伤细胞和细胞毒性T淋巴细胞基因的表达存在差异。我们的研究结果表明，TS组和对照组之间存在与年龄相关的干扰素、免疫和蛋白质降解基因表达差异。
