El Mokhtari N E, Ott S J, Nebel A, Simon R, Schreiber S
Department of Cardiology, University Hospital Schleswig-Holstein, UKSH Campus Kiel, Kiel, Germany.
Int J Immunogenet. 2006 Aug;33(4):307-11. doi: 10.1111/j.1744-313X.2006.00618.x.
Infection and innate immunity have been suggested as playing an important role in the pathogenesis of atherosclerosis. The recently discovered pattern-recognition receptor (PRR) proteins initiate signalling after host-pathogen interactions and several PRRs, especially the Toll-like receptor 4 (TLR4), have been shown to be involved in the development and progression of atherosclerosis. A new addition to the PRRs is CARD4, a gene that encodes the protein nucleotide-binding oligomerization domain 1 (NOD1) and that seems to be associated with barrier function in chronic inflammatory disorders. Recently, a functional variant in the CARD4 gene, the insertion-deletion polymorphism ND(1)+32656, has been associated with inflammatory barrier diseases (inflammatory bowel diseases and asthma). We analysed the frequencies of this known functional mutation in the CARD4 gene and of the two adjacent variants, rs2075822 and rs2907748, in a German sample of 1440 unrelated early onset coronary heart disease (CHD) patients and healthy controls. Genotype and haplotype data showed no evidence for a significant association of these CARD4 variants with CHD. Our results suggest that the analysed CARD4 mutations do not play a major role in the aetiology of CHD.
感染和先天免疫被认为在动脉粥样硬化的发病机制中起重要作用。最近发现的模式识别受体（PRR）蛋白在宿主与病原体相互作用后启动信号传导，并且已证明几种PRR，特别是Toll样受体4（TLR4），参与动脉粥样硬化的发生和发展。PRR家族的一个新成员是CARD4，该基因编码蛋白核苷酸结合寡聚化结构域1（NOD1），似乎与慢性炎症性疾病中的屏障功能有关。最近，CARD4基因中的一个功能性变体，即插入缺失多态性ND(1)+32656，与炎症性屏障疾病（炎症性肠病和哮喘）相关。我们在1440名无亲缘关系的早发性冠心病（CHD）患者和健康对照的德国样本中分析了CARD4基因中这种已知功能性突变以及两个相邻变体rs2075822和rs2907748的频率。基因型和单倍型数据表明，没有证据显示这些CARD4变体与CHD存在显著关联。我们的结果表明，所分析的CARD4突变在CHD的病因中不发挥主要作用。
