International Journal of Genetic Engineering 2012, 2(3): 19-27 DOI: 10.5923/j.ijge.20120203.01 Association of Periodontal Diseases with Genetic Polymorphisms Megha Gandhi*, Shaila Kothiwale KLE V K Institute of Dental Sciences, KLE University, Belgaum, Karnataka, India Abstract Periodontal diseases are multifactorial in nature. While microbial and other environmental factors are believed to initiate and modulate periodontal disease progression, there now exist strong supporting data that genetic polymorphisms play a role in the predisposition to and progression of periodontal diseases. Variations in any number or combination of genes that control the development of the periodontal tissues or the competency of the cellular and humoral immune systems could affect an individual's risk for disease. A corollary of this realization is that if the genetic basis of periodontal disease susceptibility can be understood, such information may have diagnostic and therapeutic value. This review aims to update the clinician about various genetic polymorphisms associated with periodontal diseases to aid in a better approach to the condition in the future. Ke ywo rds Periodontal Disease, Gene Polymorphisms, Chronic Periodontitis, Aggressive Periodontitis, Hereditary Gingiva l Fibro matosis the susceptibility of an individual to periodontal diseases. 1. Introduction Identifying genes and their polymorphisms can result in novel diagnostics for risk assessment, early detection o f Periodontal disease is an inflammatory illness that disease and individualized treatment approaches[6]. Thus, represents the main cause of tooth loss in developed genetic epidemiology, including knowledge of genetic countries, with increasing prevalence in the developing polymorphisms, holds promise as one of the tools that may world [1]. Periodontitis is defined as “an inflammatory contribute to the understanding of periodontal disease (Fig disease of the supporting tissues of the teeth caused by 2). specific microorganisms or groups of specific microorganisms, resulting in progressive destruction of the periodontal ligament and alveolar bone with pocket 2. Evidence for the Role of Genetics in formation, recession, or both[2]. Changes that occur in the Periodontal Disease alveolar bone are crucial because the destruction of bone is responsible for tooth loss. Periodontal diseases are Periodontal research has greatly expanded to elucidate the multifactorial in nature. While microbial and other role of genetics in periodontal disease states. Consequently, environmental factors are believed to initiate and modulate there has been great interest in identifying allelic variants of periodontal disease progression, there now exists strong genes that can be used to assess disease risk for periodontal supporting data that genetic and environmental risk factors diseases. Reports of genetic polymorphisms associated with play a role in the predisposition to and progression of periodontal disease are continuously increasing (Fig 3). periodontal diseases (Fig 1)[3,4,5]. In the past it was thought that periodontitis would The application of genetic information and technology for eventually develop in subjects with a longstanding history of the prediction, diagnosis and treatment of periodontal poor oral hygiene and gingivitis[7]. Despite this belie f, it was conditions is conceptually compelling. Several features like recognized that only a portion of the variability of disease in cytokines, cell-surface receptors, chemokines, enzymes and the population could be explained by environmental factors others that are related to antigen recognition, the immune alone. This variation must have been attributable to either system, host response, among others, are determined by unrecognized components of the environment or differences genetic components; polymorphisms of which may increase among individuals in their susceptibilities to disease. Because host susceptibility may be defined in terms of * Corresponding author: genetic variation, the focus of determining disease [email protected] (Megha Gandhi) susceptibility shifted to quantify the genetic aspects of Published online at http://journal.sapub.org/ijge Copyright © 2012 Scientific & Academic Publishing. All Rights Reserved disease. Epidemiologic studies as well as longitudinal 20 Megha Gandhi et al.: Association of Periodontal Diseases with Genetic Polymorphisms clinical studies of the oral microbial flora supported the environmental factors are required for periodontitis, the development of the theory that although microbial and disease may have a genetic background (Fig 4). Fi gure 1. Model for pathogenesis of human periodontal diseases. (Modified from Page RC, Kornman KS. The pathogenesis of human periodontitis: an int roduction. Periodontol 2000 1997; 14: 9-11) Fi gure 2. Relationship between genetic diagnosis and target genes at various stages of periodontitis and their treatment strategy. Each stage of the periodontal disease progression can be assessed based on a genetic diagnosis and treatment can be aimed for the target genes expressed at that stage of disease. (Modified from Takashiba S, Naruishi K. Gene polymorphisms in periodont al health and disease. Periodontol 2000 2006; 40: 94–106) International Journal of Genetic Engineering 2012, 2(3): 19-27 21 Fi gure 3. Genetic factors in periodontitis and their potential biologic influence. Candidate genetic factors with definite influence on disease states (shown in dashed circles); pot ent ial fact ors with inadequat e data to prove associat ion with disease (shown in dott ed circles) Fi gure 4. Effect of multiple assaults of environment al fact ors on disease progression and the effect of increased predisposit ion caused by genet ic factors a. Periodontit is suscept ibility may be regulat ed by a gene polymorphism (dott ed line) without ever result ing in developing overt disease. Hence, perio do nt it is symptoms might be unaffected by a gene polymorphism. However, with multiple effects of environmental factor assaults, the disease may become apparent (solid line from factors A-D). b. Increased predisposition towards periodontal disease may also result as a funct ion of the basal predisposit ion (dott ed line). Hence, higher “predisposition” leads to increased disease activity. as a result of these effects, rate of disease progression (elbow-shaped line) rises significant ly following each environmental assault. (Modified from Takashiba S, Nar uish i K. Gene polymorphisms in periodontal health and disease. Periodontol 2000 2006; 40: 94–106) A study was done as early as 1966 in over 1800 subjects a relatively high prevalence in subjects with gingivitis or which deduced that certain individuals were more at risk for minor periodontitis as compared to severe forms. Therefore, developing periodontitis than others.[8] The same the existence of high-risk groups could not be explained by phenomenon was found in two longitudinal studies the microbiology alone. These high-risk groups represented evaluating the effect of periodontal therapy in patients around 10-15% of the population, in whom the disease suffering fro m periodontitis for more than 15 years[9,10]. In quickly progressed from chronic gingivitis to destructive a classic longitudinal study of the natural history of periodontitis[12,13]. periodontitis, Loe et al (1986) found that a relatively sma ll This differential risk for periodontitis was consistent with proportion of the population is at risk for developing severe heritable elements of susceptibility and it is possible that forms of periodontitis suggested that not everybody is periodontitis may be explained by several tens of equally susceptible to periodontitis[11]. relatively common high-risk polymorphisms with The microbial causation of inflammatory periodontal cumulative high-susceptibility profiles[6]. Most genetic diseases was well established[7,11]. However, it was research in periodontitis has now focused on gene debated that if periodontitis was simply and solely caused by polymorphisms that play a role in immunoregulation or one or more specific periodontal pathogens, the disease metabolism, such as cytokines, cell-surface receptors, should have developed in majority of subjects infected by chemokines, enzymes and others that are related to antigen these organisms. In contrast, periodontal pathogens showed recognition (Table 1). 22 Megha Gandhi et al.: Association of Periodontal Diseases with Genetic Polymorphisms Ta b l e 1. Var i o u s gene polymorphisms which have been investigated for t heir role in periodontal disease Cytokines And Metabolism-Related Antigen Recognition-Relate d Immunorece ptors-Rela te Miscellaneous Gene Chemokine Receptor Receptor Polymorphisms d Pol ymorphisms Polymorphisms Polymorphisms Polymorphisms Int erleukins (IL–1, –2, –4, Vitamin D Receptor Fc-Gamma Receptor Angiotensin-convert i Human leukocyt e ant igens (HLA) –6, –10) (VDR) (FCγR) ng enzyme (ACE) T umo r necrosis fact or Cathepsins (CTS–B, –D, Calprot ect in CD14 molecule Type 1 collagen (T NF) –G, –L) n-formyl-L-methionyl-L-leucyl-L En doth elial n it ric Transforming growth N-acet yltransferase 2 Toll-like receptor (TLR-2, -phenylalanine (nFMLP) / Formyl oxide synt hase factor–β (T GF–β) (NAT2) -4) pept ide receptor (FPR) (eNOS) Mat rix Int erleukin-enhancing Prostaglandin-fam ily metalloproteinases Estrogen receptor-2 binding fact or (ILF) (PT G) (MMP s) Tissue inhibit or of IL–6 signal transducer Hydroprostaglandin metalloproteinases Fibrinogen (IL6ST) dehydrogenase