BACKGROUND Global gene expression levels are known to be highly dependent upon gross demographic features including age, yet identification of age-related genomic indicators has yet to be comprehensively undertaken in a disease and treatment-specific context. METHODS We used gene expression data from CD4+ lymphocytes in the Asthma BioRepository for Integrative Genomic Exploration (Asthma BRIDGE), an open-access collection of subjects participating in genetic studies of asthma with available gene expression data. Replication population participants were Puerto Rico islanders recruited as part of the ongoing Genes environments & Admixture in Latino Americans (GALA II), who provided nasal brushings for transcript sequencing. The main outcome measure was chronic asthma control as derived by questionnaires. Genomic associations were performed using regression of chronic asthma control score on gene expression with age in years as a covariate, including a multiplicative interaction term for gene expression times age. RESULTS The SMARCD1 gene (SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily D member 1) interacted with age to influence chronic asthma control on inhaled corticosteroids, with a doubling of expression leading to an increase of 1.3 units of chronic asthma control per year (95% CI [0.86, 1.74], p = 6 × 10- 9), suggesting worsening asthma control with increasing age. This result replicated in GALA II (p = 3.8 × 10- 8). Cellular assays confirmed the role of SMARCD1 in glucocorticoid response in airway epithelial cells. CONCLUSION Focusing on age-dependent factors may help identify novel indicators of asthma medication response. Age appears to modulate the effect of SMARCD1 on asthma control with inhaled corticosteroids.

中文翻译：

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SMARCD1 的表达与年龄相互作用，与吸入皮质类固醇治疗的哮喘控制相关。

背景技术已知全球基因表达水平高度依赖于总体人口统计特征，包括年龄，但尚未在疾病和治疗特定的背景下全面进行年龄相关基因组指标的鉴定。方法我们使用来自哮喘生物库中的 CD4+ 淋巴细胞的基因表达数据进行整合基因组探索 (Asthma BRIDGE)，这是一个开放获取的参与哮喘遗传研究的受试者集合，具有可用的基因表达数据。复制人群参与者是波多黎各岛民，他们作为拉丁美洲裔美国人正在进行的基因环境和混合 (GALA II) 的一部分招募，他们为转录本测序提供鼻刷。主要结果指标是通过问卷调查得出的慢性哮喘控制。使用慢性哮喘控制评分对基因表达的回归与年龄作为协变量进行基因组关联，包括基因表达乘以年龄的乘法交互项。结果 SMARCD1 基因（染色质亚家族 D 成员 1 的 SWI/SNF 相关基质相关肌动蛋白依赖性调节因子）与年龄相互作用影响慢性哮喘对吸入皮质类固醇的控制，表达加倍导致慢性哮喘增加 1.3 个单位。每年哮喘控制情况（95% CI [0.86, 1.74]，p = 6 × 10-9），表明随着年龄的增长哮喘控制会恶化。该结果在 GALA II 中重复（p = 3.8 × 10-8）。细胞分析证实了 SMARCD1 在气道上皮细胞糖皮质激素反应中的作用。结论 关注年龄相关因素可能有助于确定哮喘药物反应的新指标。年龄似乎可以调节 SMARCD1 对吸入皮质类固醇哮喘控制的影响。