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.
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。