Interactions of lymphotoxin α (TNF-β), angiotensin-converting enzyme (ACE), and endothelin-1 (ET-1) gene polymorphisms in adult periodontitis

Background: Adult periodontitis is a complex multifactorial disease whose etiology is not well defined. To investigate whether the genes encoded within the HLA class III region may confer susceptibility to periodontitis, polymorphisms in the ET-1 and TNF-beta genes were analyzed together with the I/D polymorphism of the ACE gene. Methods: We determined allele and genotype frequencies of the NcoI bi-allelic polymorphism of the TNF-beta gene, the I/D (insertion/deletion) polymorphism of the ACE gene, and the TaqI polymorphism of the ET-1 gene in 63 Caucasian patients with adult periodontitis and 95 orally healthy controls. Results: We found a significant difference in a 3 locus combination of genotypes between patients and controls (P <0.05). In the next analyses, no significant differences were found in allele frequencies of single genes, but we did find a significant difference in the genotype distribution between cases and controls for TNF-<beta> (P<0.03). Differences were also observed for 2 locus combinations of ACE and TNF-<beta> genotypes (P <0.03), and the ET-1 and TNF-<beta> (P <0.05) genes. Evidence of deviation from Hardy-Weinberg equilibrium was observed in the periodontitis group for TNF-<beta>, with an absence of the B1B1 homozygotes in patients. Conclusions: This study is of an exploratory nature. Considering the number of significant results, however, at least a part of the observed associations may obviously be real and our findings suggest that interactions of the TNF-beta, ET-1, and ACE genes may be involved in susceptibility to adult periodontitis.