Identification of genetic risk factors for periodontitis and possible mechanisms of action

Abstract

Mutations in the cathepsin C gene (CTSC) have been identified as causal for the Papillon-Lefèvre syndrome (PLS), which includes prepubertal periodontitis (PP). Some CTSC mutations are causal for PP without PLS. No relationship has been demonstrated between CTSC mutations and other forms of periodontitis. Genetic polymorphisms in a candidate gene approach have been explored as risk factors for periodontitis. There is limited evidence that some polymorphisms in the genes encoding interleukins (IL)-1, Fc gamma receptors (Fc gammaR), IL-10 and the vitamin D receptor, may be associated with periodontitis in certain ethnic groups. However relatively large variations in carriage rates of the Rare (R)-alleles among studies on any polymorphism were observed. The available studies appear under-powered and do not adequately take into account other pertinent risk factors for periodontitis. Future studies should include larger cohorts, should clearly define phenotypes and should adequately control for other risk factors. In addition to the candidate gene approach, alternative strategies need to be considered to elucidate the gene variations, which confer risk for periodontitis.

Gene–gene interaction among cytokine polymorphisms influence susceptibility to aggressive periodontitis

“…6 However, most studies showed variable and inconclusive correlations between the presence of the disease and the tested single-nucleotide polymorphisms (SNPs) in both forms of periodontitis. 7 These findings might be consistent with the hypothesis, debated by Moore 8 and Templeton, 9 that epistasis is likely to be a ubiquitous component of the genetic architecture of common human diseases, in general, and AgP in particular. In other words, it may be that the positive results from different studies in terms of the association between of single polymorphisms and AgP do not replicate across independent samples because of epistasis.…”

“…As complex diseases, such as periodontitis, are typically polygenic, 23 they are associated with variations in multiple genes, each providing a small overall contribution to the disease susceptibility and to the severity of the pathologic process. Similarly to other complex diseases, Loos et al 7 estimated at least 10, and as high as 20, modifying disease genes involved in periodontitis susceptibility. There have been some early attempts to analytically search for epistatic effects in the pathogenetic pathway of periodontitis, 24,25 but some of these genetic effects may be undetectable by current single-locus methodology.…”

TBX21-1993T/C (rs4794067) polymorphism is associated with increased risk of chronic periodontitis and increased T-bet expression in periodontal lesions, but does not significantly impact the IFN-g transcriptional level or the pattern of periodontophatic bacterial infection

“…3 While microbial and environmental factors (lifestyle factors [as smoking and stress] or acquired diseases [as diabetes]) characteristically modulate host responses (and consequently periodontitis outcome), studies suggest that as much as 50% of the risk of disease can be determined by genetic factors, [4][5][6] and that numerous disease modifying genes may be involved in the pathogenesis of periodontal diseases by modulating the host's response and his susceptibility to infection. 3,7,8 Recently, the interaction between host genetic factors that can impact the ability of pathogens to invade and proliferate on host's tissues has been termed infectogenomics. 9 This concept highlights the close and intimate dependence of the host's immune mechanisms and the commensal and/or pathogenic microflora, which co-evolved in a mutually dependent fashion.…”

Genes and Gene Polymorphisms Associated with Periodontal Diesases

“…IL-1 gen polimorfizminin periodontitis veya periodontal doku yıkımının şiddeti için risk faktörü olarak tanımlanamaya-cağı ileri sürülmüştür. 44 IL-1 gibi periodontitisin patogenezinde önemli role sahip olan TNF-α'nın gen polimorfizmi ile periodontitis arasındaki ilişkiyi değerlendiren çalışmalara göre TNF-α geninin allel sıklığı da IL-1 gibi farklı etnik toplumlarda çeşitlilik gös-termektedir. TNF-α gen polimorfizmi ile periodontitis arasında ilişki olduğunu belirten çalış-malara 47 karşın, ilişkinin olmadığını ileri süren çalışmalar da [47][48][49][50][70][71][72][73] bulunmaktadır.…”