SNPs in TNFa and the one-year cardiovascular outcome in patients with coronary heart disease

Background: The aim of this subanalysis of the longitudinal cohort study (ClinicalTrials.gov Identifier: NCT01045070) was to evaluate the prognostic importance of genetic variants of tumor necrosis factor alpha (TNFa) gene for secondary cardiovascular events. Patients and methods: At baseline a total of 942 consecutive patients with angiographically proven coronary heart disease were prospectively included (Martin-Luther-University Halle-Wittenberg, Clinic of Internal Medicine III). All patients were evaluated periodontally regarding plaque index, bleeding on probing, probing depth and clinical attachment level. The one-year cardiovascular outcome of the patients was evaluated considering the predefined, combined, primary endpoint (cardiovascular death, myocardial infarction, and stroke/TIA as the). Single nucleotide polymorphisms (SNPs) c.-308G>A, c.-238G>A of TNFa gene were genotyped by CTS-PCR-SSP Tray kit (Heidelberg, Germany). Results: 941 cardiovascular patients were evaluated in the one year follow-up regarding secondary cardiovascular events (7.2% suffered from cardiovascular events: 2.0% myocardial infarction, 1.7% stroke/TIA, 3.5% cardiovascular death). Using Kaplan-Meier and log-rank Tests neither the genotype, allele and the haplotype constellation of TNFa polymorphisms (c.-308G>A and c.-238G>A) nor the presence of severe periodontal disease could be proven as significant predictors of secondary cardiovascular events. Only the occurrence of diabetes mellitus (Hazard ratio 1.85) and an higher BMI (Hazard ratio 0.943) were significantly associated with secondary cardiovascular events in a complex risk model (cox regression). Conclusions: Genetic variants of TNFa gene, namely c.-308G>A and c.-238G>A, as well as the occurrence of severe periodontal disease could not be proven as significant predictors for secondary cardiovascular events in the one year follow-up. Keywords: TNFa, SNPs, coronary heart disease, periodontitis, prognostic markers