title: Genetic variants in genes of the inflammatory response in association with infective endocarditis.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institut für Laboratoriums- und Transfusionsmedizin, Herz- und Diabeteszentrum Nordrhein-Westfalen, Universitätsklinikum der Ruhr-Universität Bochum, Bad Oeynhausen, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Weinstock
authors.affiliation: Institut für Laboratoriums- und Transfusionsmedizin, Herz- und Diabeteszentrum Nordrhein-Westfalen, Universitätsklinikum der Ruhr-Universität Bochum, Bad Oeynhausen, Germany.
authors.forename: Imke
authors.initials: I
authors.lastname: Grimm
authors.affiliation: Institut für Laboratoriums- und Transfusionsmedizin, Herz- und Diabeteszentrum Nordrhein-Westfalen, Universitätsklinikum der Ruhr-Universität Bochum, Bad Oeynhausen, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Dreier
authors.affiliation: Institut für Laboratoriums- und Transfusionsmedizin, Herz- und Diabeteszentrum Nordrhein-Westfalen, Universitätsklinikum der Ruhr-Universität Bochum, Bad Oeynhausen, Germany.
authors.forename: Cornelius
authors.initials: C
authors.lastname: Knabbe
authors.affiliation: Institut für Laboratoriums- und Transfusionsmedizin, Herz- und Diabeteszentrum Nordrhein-Westfalen, Universitätsklinikum der Ruhr-Universität Bochum, Bad Oeynhausen, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Vollmer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood*; D002116:Calcitonin / Q000097:blood / Q000235:genetics; D015740:Calcitonin Gene-Related Peptide; D019040:E-Selectin / Q000097:blood / Q000235:genetics; D004696:Endocarditis / Q000097:blood / Q000235:genetics* / Q000473:pathology; D016983:Enterococcus / Q000472:pathogenicity; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000235:genetics* / Q000473:pathology; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood / Q000235:genetics; D053583:Interleukin-1beta / Q000097:blood / Q000235:genetics; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011498:Protein Precursors / Q000097:blood / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics
chemical_list: D015415:Biomarkers; C000606589:CALCA protein, human; D019040:E-Selectin; D053583:Interleukin-1beta; D015850:Interleukin-6; D011498:Protein Precursors; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide