Chen E, Miller G E, Walker H A, Arevalo J M, Sung C Y, Cole S W
University of British Columbia, Department of Psychology, Vancouver, British Columbia, Canada.
Thorax. 2009 Jan;64(1):38-43. doi: 10.1136/thx.2007.095091. Epub 2008 Nov 10.
Low socioeconomic status (SES) is one of the most robust social factors associated with disease morbidity, including more severe asthma in childhood. However, our understanding of the biological processes that explain this link is limited. This study tested whether the social environment could get "under the skin" to alter genomic activity in children with asthma.
Two group design of children with physician diagnosed asthma who came from low or high SES families.
Genome-wide transcriptional profiles from T lymphocytes of children with asthma.
Children with asthma from a low SES background showed overexpression of genes regulating inflammatory processes, including those involved in chemokine activity, stress responses and wound responses, compared with children with asthma from a high SES background. Bioinformatic analysis suggested that decreased activity of cyclic AMP response element binding protein and nuclear factor Y and increased nuclear factor kappaB transcriptional signalling mediated these effects. These pathways are known to regulate catecholamine and inflammatory signalling in immune cells.
This study provides the first evidence in a sample of paediatric patients diagnosed with asthma that the larger social environment can affect processes at the genomic level. Specifically, gene transcription control pathways that regulate inflammation and catecholamine signalling were found to vary by SES in children with asthma. Because these pathways are the primary targets of many asthma medications, these findings suggest that the larger social environment may alter molecular mechanisms that have implications for the efficacy of asthma therapeutics.
社会经济地位低下是与疾病发病率相关的最显著社会因素之一,包括儿童期更严重的哮喘。然而,我们对解释这种关联的生物学过程的理解有限。本研究测试了社会环境是否会“深入皮肤”改变哮喘儿童的基因组活性。
对来自社会经济地位低或高家庭且经医生诊断患有哮喘的儿童进行两组设计研究。
与社会经济地位高的哮喘儿童相比,社会经济地位低的哮喘儿童T淋巴细胞的全基因组转录谱显示,调节炎症过程的基因过度表达,包括那些参与趋化因子活性、应激反应和伤口反应的基因。生物信息学分析表明,环磷酸腺苷反应元件结合蛋白和核因子Y的活性降低以及核因子κB转录信号增强介导了这些效应。已知这些途径调节免疫细胞中的儿茶酚胺和炎症信号。
本研究在被诊断患有哮喘的儿科患者样本中首次提供了证据,证明更大的社会环境可在基因组水平上影响相关过程。具体而言,发现调节炎症和儿茶酚胺信号的基因转录控制途径在哮喘儿童中因社会经济地位而异。由于这些途径是许多哮喘药物的主要靶点,这些发现表明更大的社会环境可能会改变对哮喘治疗效果有影响的分子机制。