Sex-biased Gene Expression Underlies Immune Dysfunction in Asthma.

IF 5.9 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Shannon Kay, Haseena Rajeevan, Moeun Son, Jason Kwah, Maria Ramirez, Yunqing Liu, Zuoheng Wang, Xiting Yan, Gustavo Nino, Clemente Britto, Geoffrey Chupp, Jose L Gomez
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Abstract

Asthma prevalence and severity differs between males and females across the lifespan. Pre-pubescent males are more likely to experience asthma, but females are disproportionately affected after puberty with higher symptom burden and decreased type 2 inflammation. However, as human male and female genomes are almost identical, it is especially difficult to identify differentially expressed genes by sex to account for differences in disease susceptibility and manifestations without large sample sizes. Although several genes and genetic polymorphisms lead to sex-specific effects in asthma risk, the effects of sex-biased gene expression on clinical features within patients with asthma remain understudied. In this study, we characterized gene expression differences between females and males through meta-analysis of transcriptomes of blood samples from adult patients with and without asthma in a large gene expression database (n=3,639, 56% female). A separate, local validation cohort (n=132, 78% female) identified clinical correlations with expression levels of sex-biased expressed genes. We identified 61 genes differentially expressed by sex in circulating immune cells that are unique to adult subjects with asthma and correlate with important clinical features of asthma. These genes are implicated in lymphocyte proliferation and differentiation, as well as innate and adaptive immune allergic responses in the lung. In addition, similar transcriptional meta-analyses of pediatric asthma demonstrated age-specific gene expression effects. In summary, our findings support a sex-specific inflammatory architecture in asthma that is associated with differential gene expression in the blood and is age-specific.

性别偏倚的基因表达是哮喘免疫功能障碍的基础。
在整个生命周期中,男性和女性的哮喘患病率和严重程度不同。青春期前的男性更容易患哮喘,但青春期后的女性患哮喘的比例更高,症状负担更高,2型炎症减少。然而,由于人类男性和女性基因组几乎相同,在没有大样本量的情况下,特别难以确定按性别区分的差异表达基因,以解释疾病易感性和表现的差异。尽管一些基因和遗传多态性导致哮喘风险的性别特异性效应,但性别偏倚基因表达对哮喘患者临床特征的影响仍未得到充分研究。在这项研究中,我们通过荟萃分析大型基因表达数据库(n=3,639, 56%为女性)中成年哮喘患者和非哮喘患者血液样本的转录组,表征了女性和男性之间的基因表达差异。一个单独的本地验证队列(n=132, 78%为女性)确定了与性别偏倚表达基因表达水平的临床相关性。我们在循环免疫细胞中鉴定了61个性别差异表达的基因,这些基因是成人哮喘患者所特有的,并且与哮喘的重要临床特征相关。这些基因与淋巴细胞的增殖和分化以及肺部的先天和适应性免疫过敏反应有关。此外,儿童哮喘的类似转录荟萃分析也证实了年龄特异性基因表达效应。总之,我们的研究结果支持哮喘的性别特异性炎症结构,该结构与血液中差异基因表达有关,具有年龄特异性。
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来源期刊
CiteScore
11.20
自引率
3.10%
发文量
370
审稿时长
3-8 weeks
期刊介绍: The American Journal of Respiratory Cell and Molecular Biology publishes papers that report significant and original observations in the area of pulmonary biology. The focus of the Journal includes, but is not limited to, cellular, biochemical, molecular, developmental, genetic, and immunologic studies of lung cells and molecules.
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