Weinstock Melanie, Grimm Imke, Dreier Jens, Knabbe Cornelius, Vollmer Tanja
Institut für Laboratoriums- und Transfusionsmedizin, Herz- und Diabeteszentrum Nordrhein-Westfalen, Universitätsklinikum der Ruhr-Universität Bochum, Bad Oeynhausen, Germany.
PLoS One. 2014 Oct 9;9(10):e110151. doi: 10.1371/journal.pone.0110151. eCollection 2014.
Inflammation in infective endocarditis (IE) is a complex network including interactions of inflammatory cytokines and other components of host response. Certainly, any variation in this network could influence susceptibility or disease progression of IE. In this study, 14 single nucleotide variants (SNVs) in genes coding for interleukin-1β, interleukin-6, interleukin-10, toll-like receptor-4, tumor necrosis factor-α, selectin E and intercellular adhesion molecule-1 were analyzed for an association with susceptibility to IE and correlated with disease-related laboratory parameters. Furthermore, the occurrence of SNVs was examined to elucidate pathogen-dependent associations.
The distribution of SNVs was determined in IE-patients and healthy blood donors by RFLP analysis. White blood cells (WBC) were counted using flow cytometry, concentration of C-reactive protein and procalcitonin was measured immunologically. Interleukin-6 c.471+870G>A genotypes differed significantly between IE patients and controls. The frequency of the heterozygote genotype GA was considerably higher in the patient group (68.9% vs. 43.8%, Pc<0.0003). Interleukin-6 c.-237 minor allele frequency was increased in patients, although not statistically significant. Additionally, we detected a potential relation between interleukin-1β c.315C>T and IE. Pathogen-dependent analysis showed no significantly associated subgroup in relation to IE susceptibility, but gave hints towards alterations regarding Enterococcus-caused IE cases. Patients with genotype selectin-E c.-19 GT tend to have higher preoperative WBC counts than patients with genotype GG. We further showed an association between two interleukin-1β SNVs and laboratory biomarkers.
This study shows genetic predispositions for the establishment of IE. Furthermore, correlation of SNVs with disease-related biomarkers suggests a role of genetic variants regarding the inflammatory response in IE.
感染性心内膜炎（IE）中的炎症是一个复杂的网络，包括炎性细胞因子和宿主反应的其他成分之间的相互作用。当然，这个网络中的任何变化都可能影响IE的易感性或疾病进展。在本研究中，分析了编码白细胞介素-1β、白细胞介素-6、白细胞介素-10、Toll样受体-4、肿瘤坏死因子-α、选择素E和细胞间黏附分子-1的基因中的14个单核苷酸变异（SNV）与IE易感性的关联，并与疾病相关的实验室参数相关联。此外，还检查了SNV的发生情况，以阐明病原体依赖性关联。
通过限制性片段长度多态性（RFLP）分析确定IE患者和健康献血者中SNV的分布。使用流式细胞术计数白细胞（WBC），通过免疫学方法测量C反应蛋白和降钙素原的浓度。IE患者和对照组之间白细胞介素-6 c.471+870G>A基因型存在显著差异。杂合子基因型GA在患者组中的频率显著更高（68.9%对43.8%，Pc<0.0003）。患者中白细胞介素-6 c.-237次要等位基因频率增加，尽管无统计学意义。此外，我们检测到白细胞介素-1β c.315C>T与IE之间存在潜在关系。病原体依赖性分析显示，与IE易感性无显著相关的亚组，但提示了肠球菌引起的IE病例的改变。选择素-E c.-19 GT基因型的患者术前WBC计数往往高于GG基因型的患者。我们还进一步显示了两个白细胞介素-1β SNV与实验室生物标志物之间的关联。
本研究显示了IE发生的遗传易感性。此外，SNV与疾病相关生物标志物的相关性表明基因变异在IE炎症反应中起作用。
