PDF(Pubmed)
Abstract：
BACKGROUND: The Caspase activation and recruitment domain 8 (CARD8) protein is a component of innate immunity as a negative regulator of NF- ĸB, and has been associated with regulation of proteins involved in inflammation. Expression of CARD8 mRNA and protein has been identified in human atherosclerotic lesions, and the truncated T30A variant (rs2043211) of CARD8 has been associated with lower C-reactive (CRP) and MCP-1 levels in myocardial infarction patients. The present study examines the role of a genetic variation in the CARD8 gene in relation to a selection of markers of inflammation.
METHODS: In a cross-sectional study of young healthy individuals (18.0-25.9 yrs, n = 744) the association between the rs2043211 variant in the CARD8 gene and protein markers of inflammation was assessed. Genotyping of the CARD8 C10X (rs2043211) polymorphism was performed with TaqMan real time PCR on DNA from blood samples. Protein levels were studied via Olink inflammation panel ( https://olink.com/ ). Using linear models, we analyzed men and two groups of women with and without estrogen containing contraceptives separately, due to previous findings indicating differences between estrogen users and non-estrogen using women. Genotypes were analyzed by additive, recessive and dominant models.
RESULTS: The minor (A) allele of the rs2043211 polymorphism in the CARD8 gene was associated with lower levels of CCL20 and IL-6 in men (CCL20, Additive model: p = 0.023; Dominant model: p = 0.016. IL-6, Additive model: p = 0.042; Dominant model: p = 0.039). The associations remained significant also after adjustment for age and potential intermediate variables.
CONCLUSIONS: Our data indicate that CARD8 may be involved in the regulation of CCL20 and IL-6 in men. No such association was observed in women. These findings strengthen and support previous in vitro data on IL-6 and CCL20 and highlight the importance of CARD8 as a factor in the regulation of inflammatory proteins. The reason to the difference between sexes is however not clear, and the influence of estrogen as a possible factor important for the inflammatory response needs to be further explored.
METHODS: In a cross-sectional study of young healthy individuals (18.0-25.9 yrs, n = 744) the association between the rs2043211 variant in the CARD8 gene and protein markers of inflammation was assessed. Genotyping of the CARD8 C10X (rs2043211) polymorphism was performed with TaqMan real time PCR on DNA from blood samples. Protein levels were studied via Olink inflammation panel ( https://olink.com/ ). Using linear models, we analyzed men and two groups of women with and without estrogen containing contraceptives separately, due to previous findings indicating differences between estrogen users and non-estrogen using women. Genotypes were analyzed by additive, recessive and dominant models.
RESULTS: The minor (A) allele of the rs2043211 polymorphism in the CARD8 gene was associated with lower levels of CCL20 and IL-6 in men (CCL20, Additive model: p = 0.023; Dominant model: p = 0.016. IL-6, Additive model: p = 0.042; Dominant model: p = 0.039). The associations remained significant also after adjustment for age and potential intermediate variables.
CONCLUSIONS: Our data indicate that CARD8 may be involved in the regulation of CCL20 and IL-6 in men. No such association was observed in women. These findings strengthen and support previous in vitro data on IL-6 and CCL20 and highlight the importance of CARD8 as a factor in the regulation of inflammatory proteins. The reason to the difference between sexes is however not clear, and the influence of estrogen as a possible factor important for the inflammatory response needs to be further explored.
摘要：
背景：Caspase激活和募集域8（CARD8）蛋白是先天免疫的组成部分，是NF-κB的负调节因子，并与参与炎症的蛋白质的调节有关。CARD8mRNA和蛋白质的表达已在人动脉粥样硬化病变中得到鉴定，CARD8的截短的T30A变体（rs2043211）与心肌梗死患者的C反应（CRP）和MCP-1水平降低有关。本研究检查了CARD8基因中遗传变异与选择炎症标志物有关的作用。
方法：在一项对年轻健康个体(18.0-25.9岁，n=744）评估了CARD8基因中rs2043211变体与炎症蛋白标志物之间的关联。使用TaqMan实时PCR对来自血液样品的DNA进行CARD8C10X(rs2043211)多态性的基因分型。通过Olink炎症小组(https://olink.com/)研究蛋白质水平。使用线性模型，我们分别分析了有和没有含雌激素的避孕药的男性和两组女性，由于先前的发现表明雌激素使用者和非雌激素使用者之间存在差异。基因型通过加性分析，隐性和显性模型。
结果：CARD8基因中rs2043211多态性的次要（A）等位基因与男性中CCL20和IL-6的较低水平相关（CCL20，加性模型：p=0.023；显性模型：p=0.016。IL-6,加性模型:p=0.042;显性模型:p=0.039)。在调整了年龄和潜在的中间变量后，相关性仍然很重要。
结论：我们的数据表明CARD8可能参与男性CCL20和IL-6的调节。在女性中未观察到这种关联。这些发现加强并支持了先前关于IL-6和CCL20的体外数据，并强调了CARD8作为炎症蛋白调节因子的重要性。然而，性别差异的原因尚不清楚，雌激素作为炎症反应的重要因素的影响需要进一步探讨。
方法：在一项对年轻健康个体(18.0-25.9岁，n=744）评估了CARD8基因中rs2043211变体与炎症蛋白标志物之间的关联。使用TaqMan实时PCR对来自血液样品的DNA进行CARD8C10X(rs2043211)多态性的基因分型。通过Olink炎症小组(https://olink.com/)研究蛋白质水平。使用线性模型，我们分别分析了有和没有含雌激素的避孕药的男性和两组女性，由于先前的发现表明雌激素使用者和非雌激素使用者之间存在差异。基因型通过加性分析，隐性和显性模型。
结果：CARD8基因中rs2043211多态性的次要（A）等位基因与男性中CCL20和IL-6的较低水平相关（CCL20，加性模型：p=0.023；显性模型：p=0.016。IL-6,加性模型:p=0.042;显性模型:p=0.039)。在调整了年龄和潜在的中间变量后，相关性仍然很重要。
结论：我们的数据表明CARD8可能参与男性CCL20和IL-6的调节。在女性中未观察到这种关联。这些发现加强并支持了先前关于IL-6和CCL20的体外数据，并强调了CARD8作为炎症蛋白调节因子的重要性。然而，性别差异的原因尚不清楚，雌激素作为炎症反应的重要因素的影响需要进一步探讨。
