Genes and Gene Polymorphisms Associated with Periodontal Disease

Abstract

ABSTRACT:The scientific literature during the last ten years has seen an exponential increase in the number of reports claiming links for genetic polymorphisms with a variety of medical diseases, particularly chronic immune and inflammatory conditions. Recently, periodontal research has contributed to this growth area. This new research has coincided with an increased understanding of the genome which, in turn, has permitted the functional interrelationships of gene products with each other and with environmental agents to be understood. As a result of this knowledge explosion, it is evident that there is a genetic basis for most diseases, including periodontitis. This realization has fostered the idea that if we can understand the genetic basis of diseases, genetic tests to assess disease risk and to develop etiology-based treatments will soon be reality. Consequently, there has been great interest in identifying allelic variants of genes that can be used to assess disease risk for periodontal diseases. Reports of genetic polymorphisms associated with periodontal disease are increasing, but the limitations of such studies are not widely appreciated. While there have been dramatic successes in the identification of mutations responsible for rare genetic conditions, few genetic polymorphisms reported for complex genetic diseases have been demonstrated to be clinically valid, and fewer have been shown to have clinical utility. Although geneticists warn clinicians on the over-enthusiastic use and interpretation of their studies, there continues to be a disparity between the geneticists and the clinicians in the emphasis placed on genes and genetic polymorphism associations. This review critically reviews genetic associations claimed for periodontal disease. It reveals that, despite major advances in the awareness of genetic risk factors for periodontal disease (with the exception of periodontitis associated with certain monogenetic conditions), we are still some way from determining the genetic basis of both aggressive and chronic periodontitis. We have, however, gained considerable insight into the hereditary pattern for aggressive periodontitis. Related to our understanding that it is autosomal-dominant with reduced penetrance comes a major clinically relevant insight into the risk assessment and screening for this disease, in that we appreciate that parents, offspring, and siblings of patients affected with aggressive periodontitis have a 50% risk of this disease also. Nevertheless, we must exercise caution and proper scientific method in the pursuit of clinically valid and useful genetic diagnostic tests for chronic and aggressive periodontitis. We must plan our research using plausible biological arguments and carefully avoid the numerous bias and misinterpretation pitfalls inherent in researching genetic associations with disease.

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

“…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. 26 One of the early definitions of epistasis was based on additivity in a linear model.…”

Linkage disequilibrium analysis of case–control data: an application to generalized aggressive periodontitis

“…18 Recently, some comprehensive and detailed reviews have presented convincing evidence for heritable components of both susceptibility and progression (or severity) of periodontal diseases. [19][20][21][22][23] Many studies have focused on the potential role of several cytokines involved in the inflammatory response, among which some of the most investigated are the IL-1a, IL-1b and IL-1Ra, [24][25][26][27][28] genes which are all located on the long arm of chromosome 2 (region 2q13-14).…”

“…22,23 Given the complex biology of IL-1 regulation and the extensive polymorphisms in the IL-1 gene cluster, it is likely that if IL-1 genes influence disease, then combinations of specific alleles will be important rather than individual alleles. Therefore, it is considered that knowledge of LD and population haplotypes in the IL-1 cluster will greatly aid rational design of experiments.…”

A nonconservative, coding single-nucleotide polymorphism in the N-terminal region of lactoferrin is associated with aggressive periodontitis in an African-American, but not a Caucasian population

“…A number of studies have examined links between polymorphisms within host-response factors and aggressive periodontitis. 25 These include examination of genes encoding inflammatory cytokines such as IL-1 and TNF-a, the anti-inflammatory cytokine IL-10 and the Fc-gamma receptor. The data thus far from these studies appear to be controversial, with a number of studies revealing associations and others showing contradictory data.…”

“…The results presented here show a novel strong association with the lactoferrin gene, adding to the growing evidence that genes play a role in the predisposition to and progression of periodontal disease. 18,21,[25][26][27] The data presented in this study describe a novel, functional single-nucleotide polymorphism that goes some way to help explain the genetic susceptibility associated with aggressive periodontitis in African Americans. It may be that the polymorphism described here affects the ability of lactoferrin to bind to and/or kill different genetic variants of bacteria, including Aa, that have previously been implicated with the pathogenicity in aggressive periodontitis.…”