Polymorphism of CD14 Gene Is Associated with Adverse Outcome among Patients Suffering from Cardiovascular Disease

Abstract

Background. The biological link between severe periodontitis and cardiovascular disease is well established. Both complex inflammatory diseases are influenced by genetic background. Therefore, the impact of genetic variations of receptors of the innate immune system—(Toll-like receptors (TLRs)) TLR2, TLR4, cluster of differentiation 14 (CD14), and the transcription factor nuclear factor-κΒ (NF-κB)—was investigated. Materials and Methods. In this study (ClinicalTrials.gov identifier: NCT01045070), 1002 cardiovascular (CV) patients were included. In a 3-year follow-up period, new vascular events were assessed. SNPs in CD14 (rs2569190), NF-κΒ (rs28362491), TLR2 (rs5743708), and TLR4 (rs4986790) were genotyped. The impact of these genetic variants on severe periodontitis as well as on CV outcome was assessed. Results. All investigated genetic variants were not associated with preexisting CV events or severe periodontitis in CV patients. In Kaplan-Meier survival analyses, the CT genotype of CD14 single-nucleotide polymorphism (SNP) rs2569190 was shown to be an independent predictor for combined CV endpoint (log rank: $p=0.035$ ; cox regression; hazard ratio: 1.572; $p=0.044$ ) as well as cardiovascular death (log rank: $p=0.019$ ; cox regression; hazard ratio: 1.585; $p=0.040$ ) after three years of follow-up. Conclusions. SNPs in CD14, NF-κΒ, TLR2, and TLR4 are no risk modulators for preexisting CV events or severe periodontitis in CV patients. The CT genotype of CD14 SNP rs2569190 provides prognostic value for further CV events within 3 years of follow-up.