Tooth Supporting Structures Disease

Tooth supporting structures disease, commonly known as periodontal disease or gum disease, refers to a group of inflammatory conditions affecting the tissues that surround and support the teeth. These structures, collectively known as the periodontium, include the gums (gingiva), the periodontal ligament, the cementum covering the tooth root, and the alveolar bone that anchors the teeth. The disease often begins as gingivitis, a reversible inflammation of the gums, and can progress to periodontitis, a more severe and irreversible condition characterized by the destruction of the bone and ligaments holding the teeth in place. It is a highly prevalent global health issue affecting a significant portion of the adult population.

Biological Basis

The primary cause of tooth supporting structures disease is the accumulation of bacterial plaque biofilm on the tooth surfaces, particularly along the gumline. The bacteria within this biofilm release toxins and initiate an inflammatory response in the host. While the presence of bacteria is essential, the progression and severity of the disease are largely determined by the individual’s immune response to these microbial challenges. Genetic factors play a crucial role in modulating this immune response, influencing an individual’s susceptibility to inflammation, tissue breakdown, and the ability to repair damaged tissues. Variations in genes related to immune regulation, inflammation, and tissue remodeling can therefore predispose individuals to more aggressive forms of periodontal disease.

Clinical Relevance

Clinically, tooth supporting structures disease manifests with symptoms such as bleeding gums, bad breath (halitosis), gum recession, increased pocket depths around the teeth, and eventually tooth mobility and tooth loss. Diagnosis involves a dental examination, measurement of periodontal pocket depths, and radiographic assessment of bone loss. Early stages, like gingivitis, can often be reversed with diligent oral hygiene and professional cleanings. However, periodontitis requires more intensive treatment, including deep cleanings (scaling and root planing), antibiotics, and sometimes surgical interventions to manage infection and reconstruct lost tissue. The disease has also been linked to various systemic health conditions, including diabetes, cardiovascular disease, respiratory conditions, and adverse pregnancy outcomes, highlighting its broader impact on overall health.

Social Importance

The widespread prevalence and potential for severe consequences make tooth supporting structures disease a significant public health concern. It impacts the quality of life by affecting an individual’s ability to eat, speak, and smile confidently, leading to social and psychological distress. The economic burden is substantial, encompassing the costs of dental treatments, lost productivity due to dental issues, and the indirect costs associated with its systemic health implications. Understanding the genetic predispositions can lead to personalized risk assessments, allowing for targeted preventive strategies and earlier interventions. Public health initiatives focused on promoting good oral hygiene, regular dental check-ups, and awareness of the disease’s risk factors are crucial for reducing its social and economic impact.

Limitations

Methodological and Statistical Considerations

Many studies investigating the genetic underpinnings of tooth supporting structures disease are constrained by their study designs and statistical power. Smaller sample sizes can limit the ability to detect genetic variants with modest effect sizes, potentially leading to an incomplete understanding of the genetic landscape. Furthermore, some initial findings may represent inflated effect sizes or false positives due to insufficient statistical rigor or the absence of independent replication in diverse cohorts. This underscores the critical need for larger, well-powered studies and rigorous validation to confirm genetic associations and ensure the robustness of discoveries.

Phenotypic Heterogeneity and Population Diversity

A significant challenge in researching tooth supporting structures disease lies in the variability of its clinical presentation and diagnostic criteria across different studies. This phenotypic heterogeneity can obscure underlying genetic signals, making it difficult to precisely map genetic contributions to specific disease subtypes or stages. Moreover, much of the genetic research has historically focused on populations of European ancestry, which restricts the generalizability of findings. The genetic architecture and allele frequencies can vary substantially across different ancestral groups, necessitating more inclusive research that encompasses diverse global populations to ensure equitable benefits from genetic insights.

Unaccounted Environmental Factors and Missing Heritability

The development of tooth supporting structures disease is influenced by a complex interplay of genetic predispositions and environmental factors, many of which are not fully captured in genetic studies. Lifestyle factors such as smoking, oral hygiene practices, diet, and systemic health conditions can significantly modulate an individual’s genetic risk, acting as confounders if not adequately accounted for. A deeper understanding of these intricate gene-environment interactions is crucial for a comprehensive etiological picture. Despite the identification of several genetic risk factors, a substantial portion of the disease’s heritability remains unexplained, indicating that many genetic influences, including rare variants, structural variations, or complex epistatic interactions, have yet to be discovered or fully characterized. This “missing heritability” highlights ongoing knowledge gaps that require further investigation using advanced genomic technologies and integrative analytical approaches.

Variants

The PDE10Agene encodes phosphodiesterase 10A, an enzyme that plays a critical role in regulating cellular signaling by breaking down cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). These cyclic nucleotides are vital secondary messengers involved in a multitude of cellular processes, including metabolism, neurotransmission, and immune responses . WhilePDE10Ais notably abundant in the brain, particularly in the striatum where it influences dopamine and glutamate pathways, its activity is also present in other tissues, contributing to the broader regulation of cellular homeostasis . Dysregulation ofPDE10A activity can therefore have widespread effects on cell function and overall physiological balance.

The single nucleotide polymorphism (SNP)rs76103501 is an intronic variant located within the PDE10Agene . Intronic variants, while not directly altering the amino acid sequence of a protein, can nonetheless significantly impact gene expression and function. Such genetic variations can influence messenger RNA (mRNA) splicing efficiency, alter binding sites for transcription factors, or affect mRNA stability, ultimately leading to changes in the amount or activity of thePDE10A enzyme . Consequently, rs76103501 may subtly modulate the overall cellular levels or enzymatic efficiency of phosphodiesterase 10A, thereby affecting the balance of cAMP and cGMP signaling pathways.

Variations in genes like PDE10Athat influence fundamental cellular signaling pathways can have implications for the health of tooth supporting structures. The cyclic nucleotide signaling pathways, regulated by enzymes such as phosphodiesterase 10A, are crucial for modulating inflammatory responses, bone remodeling, and the maintenance of connective tissues.^[1]For instance, altered cAMP/cGMP levels can affect the function of immune cells involved in periodontal inflammation, influence the activity of osteoblasts and osteoclasts critical for alveolar bone integrity, and impact the health and regeneration of periodontal ligament cells and gingival fibroblasts.^[1] Therefore, a variant like rs76103501 in PDE10A could indirectly contribute to an individual’s susceptibility to or progression of diseases affecting tooth supporting structures by subtly altering these interconnected biological processes.

Key Variants

RS ID	Gene	Related Traits
rs76103501	PDE10A	tooth-supporting structures disease

Signs and Symptoms

Initial Clinical Indicators and Subjective Experiences

The early stages of tooth supporting structures disease often manifest through localized inflammatory responses, primarily affecting the gingiva. Typical signs include gingival redness, swelling, and a tendency for bleeding, particularly during toothbrushing or professional probing.^[2] Common subjective symptoms reported by individuals can range from mild discomfort and sensitivity to the presence of halitosis (bad breath). ^[1] However, these early stages, often termed gingivitis, may also be asymptomatic, leading to delayed recognition. Assessment methods rely on visual inspection for color and contour changes, and the objective measurement of bleeding on probing (BOP), which is a crucial indicator of active inflammation. ^[3]The presence and extent of BOP, along with patient-reported symptoms, provide valuable diagnostic information for identifying initial disease activity and prompting intervention.

Inter-individual variability in the perception and presentation of these initial signs is common; some individuals may experience significant discomfort with minimal clinical signs, while others may present with pronounced inflammation yet report no pain. Age-related changes can influence the gingival response, with older individuals sometimes exhibiting a blunted inflammatory response despite underlying pathology. The diagnostic significance of these early indicators lies in their ability to serve as red flags for incipient disease, differentiating simple gingivitis from more advanced forms or other oral lesions. Early detection based on these signs and symptoms is critical for preventing progression to more destructive forms of the disease.

Objective Measures of Tissue Destruction and Functional Impairment

As tooth supporting structures disease progresses, it is characterized by the irreversible destruction of periodontal tissues, leading to clinical attachment loss and alveolar bone resorption. Objective signs include gingival recession, increased probing pocket depths (PPD), and suppuration (pus formation) from the gingival sulcus.^[4]Individuals may notice teeth appearing longer, develop increased tooth mobility, or experience changes in their bite or masticatory function. Measurement approaches are central to diagnosing the severity and extent of this destruction, primarily involving the use of a calibrated periodontal probe to measure PPD and clinical attachment level (CAL), which directly quantifies the loss of connective tissue attachment.^[5]Radiographic assessments, such as periapical radiographs, bitewing radiographs, or cone-beam computed tomography (CBCT), are indispensable for evaluating the extent of alveolar bone loss, its pattern (horizontal or vertical), and the presence of furcation involvement.^[6]

The severity of the disease is categorized based on CAL and bone loss, ranging from mild to severe, and different clinical phenotypes, such as chronic or aggressive periodontitis, exhibit distinct patterns of progression and tissue destruction. Variability is observed across individuals, with some experiencing rapid, aggressive tissue loss (e.g., in specific forms of periodontitis) while others have a slower, more chronic progression.^[7]Sex differences in disease prevalence and severity have been noted, with some studies suggesting men may have a higher prevalence or severity of periodontitis.^[8]The diagnostic value of PPD, CAL, and radiographic bone loss is paramount for confirming the diagnosis, classifying the disease stage and grade, and serving as key prognostic indicators for future tooth loss or therapeutic outcomes. These objective measures are crucial for differential diagnosis, distinguishing periodontitis from other conditions causing bone loss or tooth mobility.

Systemic Associations, Biomarkers, and Phenotypic Diversity

Tooth supporting structures disease is increasingly recognized for its complex interplay with systemic health, which can influence its presentation and progression. Atypical presentations may include unusually rapid disease progression, early onset, or resistance to conventional therapy, often signaling underlying systemic conditions such as diabetes mellitus, cardiovascular disease, or specific genetic predispositions.^[9]Beyond clinical measurements, advanced diagnostic approaches include the analysis of biomarkers in gingival crevicular fluid (GCF) or saliva, which can reflect the local inflammatory load and tissue breakdown. These biomarkers might include elevated levels of inflammatory mediators like interleukins (e.g., IL-1beta, IL-6) or matrix metalloproteinases (MMPs), which correlate with disease activity and tissue destruction.^[10] Furthermore, genetic susceptibility can play a role, with certain genetic variations, such as polymorphisms in the IL1A or IL1Bgenes, being associated with an increased risk or more severe forms of the disease.^[11]

Phenotypic diversity is significant, with individuals presenting with localized versus generalized forms of the disease, and varying rates of progression even within the same severity category. This heterogeneity underscores the importance of a comprehensive diagnostic approach that considers not only local clinical signs but also systemic health status and genetic background. The diagnostic significance of these systemic associations and biomarkers lies in their ability to provide a more holistic understanding of the disease, aiding in identifying high-risk individuals, guiding personalized treatment strategies, and offering prognostic insights beyond traditional clinical parameters. Red flags for atypical presentations necessitate a thorough medical history and potential referral for systemic evaluation.

Causes of Tooth Supporting Structures Disease

Genetic Predisposition and Inheritance

The susceptibility to tooth supporting structures disease is significantly influenced by an individual’s genetic makeup. This can manifest through various mechanisms, including inherited variants that directly impact immune responses, inflammatory pathways, or tissue repair processes. While some rare forms of the disease may follow Mendelian inheritance patterns, driven by highly penetrant mutations in specific genes, the more common presentations are often polygenic, involving the cumulative effect of multiple genetic variations, each contributing a small but significant risk. Furthermore, gene-gene interactions can play a crucial role, where the combined effect of variants in different genes may lead to a higher disease risk than the sum of their individual contributions, modulating complex biological pathways involved in disease progression.

Environmental and Lifestyle Influences

Environmental factors and lifestyle choices are critical determinants in the development and progression of tooth supporting structures disease. Poor oral hygiene, characterized by inadequate plaque control, creates a fertile ground for bacterial colonization and subsequent inflammation, directly leading to tissue damage. Lifestyle factors such as smoking are strongly associated with increased disease severity, impairing immune function and hindering healing processes. Dietary habits, particularly those high in refined sugars, can indirectly contribute by promoting bacterial growth and inflammation. Additionally, broader environmental elements like exposure to certain toxins, socioeconomic disparities influencing access to dental care, and even geographic variations in micronutrient availability or microbial strains can collectively impact an individual’s risk profile.

Gene-Environment Interactions

The development of tooth supporting structures disease is often a result of intricate gene-environment interactions, where an individual’s genetic predisposition modifies their response to environmental triggers. For example, specific genetic variants may render an individual more susceptible to the inflammatory effects of bacterial plaque or the tissue-damaging properties of tobacco smoke. Conversely, protective genetic factors might mitigate the impact of adverse environmental exposures, offering a degree of resilience. This complex interplay means that individuals with certain genetic profiles may develop severe disease even with moderate environmental challenges, while others with different genetic backgrounds might remain relatively healthy despite similar exposures, highlighting the personalized nature of disease risk.

Developmental, Epigenetic, and Systemic Factors

Beyond immediate genetic and environmental influences, a range of developmental, epigenetic, and systemic factors contribute to the etiology of tooth supporting structures disease. Early life influences, such as prenatal conditions or childhood health issues, can impact the proper development of oral tissues, potentially predisposing individuals to disease later in life. Epigenetic modifications, including DNA methylation and histone modifications, can alter gene expression without changing the underlying DNA sequence, affecting cellular responses and tissue homeostasis. Furthermore, systemic comorbidities like diabetes, cardiovascular disease, or autoimmune disorders can significantly exacerbate the disease by impairing immune function and wound healing. Certain medications, such as those causing xerostomia (dry mouth), can reduce saliva’s protective effects, while age-related physiological changes, including altered immune responses and reduced tissue regenerative capacity, naturally increase vulnerability to the disease over time.

Biological Background

Anatomy and Homeostasis of Tooth Supporting Structures

The tooth supporting structures, collectively known as the periodontium, consist of the gingiva, periodontal ligament, cementum, and alveolar bone. These specialized tissues work in concert to firmly anchor teeth within the jawbone, absorb occlusal forces, and protect the underlying bone from the oral environment. The gingiva forms a protective seal around the tooth, while the periodontal ligament, a complex network of collagen fibers, connects the cementum covering the tooth root to the alveolar bone, allowing for slight tooth movement and proprioception.

Maintaining the health and integrity of the periodontium relies on a dynamic state of homeostasis, where continuous remodeling and repair processes are balanced. Various cell types, including fibroblasts, osteoblasts, and osteoclasts, precisely regulate the synthesis and degradation of extracellular matrix components and bone. This delicate balance ensures the structural resilience of the tissues and their ability to adapt to physiological stresses, preventing both excessive tissue breakdown and overgrowth.

Cellular and Molecular Mechanisms of Inflammation

The initiation of tooth supporting structures disease is often triggered by a persistent challenge from microbial biofilms residing on the tooth surface. In response, the host immune system mounts an inflammatory reaction, involving the recruitment and activation of various immune cells such as neutrophils, macrophages, and lymphocytes. These cells are crucial for identifying and eliminating pathogens, but an uncontrolled or dysregulated response can lead to tissue damage.

At the molecular level, this inflammatory process is orchestrated by a complex interplay of signaling pathways and key biomolecules. Inflammatory cytokines, such as interleukins and tumor necrosis factor-alpha, act as critical messengers, amplifying the immune response and influencing cell behavior. Enzymes like matrix metalloproteinases (MMPs) are upregulated, leading to the breakdown of collagen and other extracellular matrix components, which are essential for tissue integrity. Receptor-ligand interactions on cell surfaces also play a vital role in regulating immune cell activation, differentiation, and the perpetuation of the inflammatory cascade.

Genetic and Epigenetic Contributions to Susceptibility

An individual’s genetic makeup significantly influences their susceptibility to tooth supporting structures disease. Genetic variations can affect the efficiency of immune responses, the intensity of inflammatory reactions, and the capacity for tissue repair and regeneration. Genes involved in cytokine production, immune cell function, and the regulation of bone metabolism can harbor polymorphisms that alter protein function or expression levels, thereby predisposing individuals to a more severe or persistent disease course.

Beyond the DNA sequence itself, epigenetic modifications contribute to the regulation of gene expression without altering the underlying genetic code. Mechanisms such as DNA methylation and histone modifications can influence whether specific genes are activated or silenced, impacting the cellular response to environmental cues. These epigenetic changes can be influenced by factors like lifestyle, diet, and microbial exposure, potentially modulating an individual’s risk and disease progression by altering the activity of genes critical for periodontal health and inflammation.

Pathophysiology and Systemic Implications

The pathophysiology of tooth supporting structures disease involves a progressive breakdown of the periodontal tissues, driven by a chronic and dysregulated host immune response to bacterial challenge. Initially, the inflammation may be reversible, but if persistent, it leads to the destruction of the periodontal ligament, resorption of the alveolar bone, and the formation of periodontal pockets around the teeth. This ongoing tissue destruction is largely mediated by the host’s own inflammatory cells and their secreted factors, which inadvertently cause collateral damage to healthy tissues.

The chronic inflammatory state within the tooth supporting structures is not confined to the oral cavity and can have broader systemic consequences. Inflammatory mediators, bacterial products, and even bacteria themselves can enter the bloodstream from the diseased periodontal tissues. This systemic dissemination of inflammatory factors can contribute to or exacerbate other chronic inflammatory conditions throughout the body, such as cardiovascular diseases, diabetes, and adverse pregnancy outcomes, highlighting the intricate connection between oral health and overall systemic well-being.

Clinical Relevance

Diagnosis and Risk Stratification

Early and accurate diagnosis of tooth supporting structures disease is crucial for effective patient management. Clinical assessment, often complemented by advanced diagnostic tools, aids in identifying the presence, extent, and severity of the disease, frequently before significant and irreversible damage occurs. This diagnostic utility allows clinicians to differentiate between various forms of the disease, enabling the selection of appropriate initial therapeutic interventions tailored to the specific presentation.

Risk stratification plays a vital role in personalized medicine and preventive dentistry. By evaluating individual risk factors, such as genetic predispositions, systemic health conditions, and lifestyle habits, clinicians can identify individuals at high risk for developing or experiencing progression of tooth supporting structures disease. This targeted approach facilitates the implementation of personalized prevention strategies, including intensified recall schedules, specific oral hygiene instructions, and early therapeutic interventions, which aim to mitigate disease onset or further advancement.

Prognosis and Treatment Management

Understanding the prognostic value of various clinical and biological markers is essential for predicting disease progression and long-term outcomes in tooth supporting structures disease. Factors such as initial disease severity, the host’s inflammatory response, and patient adherence to recommended treatment protocols significantly influence the likelihood of disease stability, recurrence, or further attachment loss. This predictive capability assists clinicians in setting realistic expectations for patients and in planning phased treatment approaches that anticipate potential challenges.

The ongoing assessment of treatment response is critical for effective disease management. Regular monitoring allows clinicians to evaluate the efficacy of therapeutic interventions, whether surgical or non-surgical, and to make necessary adjustments to the treatment plan. A poor response to initial therapy may suggest a more aggressive disease phenotype or the presence of unmanaged risk factors, prompting a re-evaluation of the strategy and potentially a shift towards more intensive or alternative therapies to improve long-term prognosis and preserve tooth function.

Systemic Associations and Complications

Tooth supporting structures disease is increasingly recognized for its bidirectional associations with various systemic health conditions, underscoring its role as an integral part of overall health. Research indicates strong links between the disease and chronic inflammatory conditions such as diabetes mellitus, cardiovascular diseases, and certain autoimmune disorders, where the oral inflammatory burden can contribute to or exacerbate systemic inflammation. A comprehensive understanding of these comorbidities is crucial for integrated patient care, often necessitating collaboration between dental and medical professionals to manage both oral and systemic health effectively.

Furthermore, the disease can manifest as a complication or an overlapping phenotype in certain syndromic presentations, frequently involving genetic predispositions that impact connective tissue integrity or immune regulation. Recognizing these associations is vital for early diagnosis in susceptible individuals and for implementing comprehensive management strategies that address both the oral manifestations and the underlying systemic condition. This integrated approach can help prevent severe complications and enhance the quality of life for affected patients.

Frequently Asked Questions About Tooth Supporting Structures Disease

These questions address the most important and specific aspects of tooth supporting structures disease based on current genetic research.

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1. My parents have gum problems. Will I definitely get them too?

Not necessarily, but you might have a higher predisposition. Genetic factors play a crucial role in how your body responds to the bacteria that cause gum disease, influencing your susceptibility to inflammation and tissue breakdown. While you might inherit some of these tendencies, it doesn’t mean you’ll definitely develop severe disease, especially with good oral hygiene. Your genes might make you more vulnerable, but lifestyle choices are also very important.

2. I brush and floss every day, but my gums still bleed. Why is that?

Even with excellent oral hygiene, some people are genetically more susceptible to gum inflammation. Variations in genes related to your immune regulation and inflammatory response can make your gums react more strongly to bacterial plaque. This means your body’s own defense system, influenced by your unique genetic makeup, might be contributing to the bleeding despite your best efforts. Regular professional cleanings are even more vital for you.

3. My breath is always bad even after brushing. Is that a sign of serious gum issues?

Yes, persistent bad breath (halitosis) can definitely be a sign of underlying gum disease. The bacteria accumulating under your gums release toxins that cause both inflammation and unpleasant odors. Your genetic predisposition can influence how severely these bacteria impact your tissues and how your body responds, potentially leading to more advanced disease and more noticeable symptoms like chronic bad breath. It’s a good idea to get it checked out by a dentist.

4. Can my gum inflammation affect other parts of my body, like my heart?

Yes, absolutely. Gum disease is linked to several systemic health conditions beyond your mouth, including cardiovascular disease, diabetes, and even respiratory conditions. The chronic inflammation and bacteria from your gums can enter your bloodstream, affecting other organs and potentially worsening existing health issues. Your genetic makeup can influence both your susceptibility to gum disease and your overall inflammatory response, which connects these dots.

5. Does what I eat make a difference for my gum health?

While genetics influence your baseline susceptibility, your diet can definitely impact your gum health by affecting your body’s overall inflammatory response. Sugary and highly processed foods can promote inflammation throughout your body, including your gums, potentially exacerbating any genetic predispositions you have. A balanced, nutrient-rich diet can support a healthier immune system, helping to mitigate some of your genetic risk.

6. I smoke, how much worse is that for my gums compared to others?

Smoking is a major risk factor that significantly amplifies your risk for severe gum disease, even more so if you have a genetic predisposition. It impairs your immune response and reduces blood flow to your gums, making them more vulnerable to bacterial attack and hindering their ability to heal. This harmful environmental factor can override or severely worsen any protective genetic traits you might have, leading to more aggressive tissue destruction.

7. Could a DNA test tell me if I’m at high risk for gum disease?

Yes, understanding your genetic predispositions through a DNA test can help assess your risk for gum disease. Variations in genes likePDE10A, which regulate cellular signaling and immune responses, can influence your susceptibility to inflammation and tissue damage. Such insights can lead to personalized risk assessments, allowing for targeted preventive strategies and earlier, more aggressive interventions tailored to your specific genetic profile.

8. My sibling has perfect gums, but mine are always inflamed. Why?

Even within the same family, individual genetic variations and how they interact with daily habits can lead to different outcomes. You and your sibling might have different variants in genes that control immune response, inflammation, or tissue repair, making one of you more susceptible. Lifestyle factors like diet, stress, or specific oral hygiene practices, even subtle ones, can also play a larger role when combined with individual genetic differences.

9. If my gums are inflamed, can I fully reverse the damage?

It depends on the stage of the disease and your genetic ability to repair tissues. Early inflammation, called gingivitis, is often fully reversible with diligent oral hygiene and professional cleaning. However, if it progresses to periodontitis, which involves bone and ligament destruction, the damage is largely irreversible. Your genes influence your body’s capacity for tissue repair and regeneration, impacting how well you can recover from damage.

10. Does my ethnic background change my risk for gum problems?

Yes, your ethnic background can influence your risk for gum problems because the genetic architecture and frequencies of risk-associated gene variants can differ across populations. Much of the genetic research has historically focused on specific groups, so the understanding of risk in diverse ancestral groups is still evolving. This means your background might be associated with unique genetic predispositions or protections.

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This FAQ was automatically generated based on current genetic research and may be updated as new information becomes available.

Disclaimer: This information is for educational purposes only and should not be used as a substitute for professional medical advice. Always consult with a healthcare provider for personalized medical guidance.

References

[1] Newman, M. G., Takei, H. H., Klokkevold, F. R., & Carranza, F. A. (2018). Carranza’s Clinical Periodontology. Elsevier.

[2] Ainamo, J., Bay, I., & Gjermo, P. (1975). The effect of toothbrushing on the development of dental plaque and gingivitis. Journal of Periodontal Research, 10(4), 180-184.

[3] Lang, N. P., & Loe, H. (1990). The relationship between plaque and gingivitis. Journal of Clinical Periodontology, 17(Suppl 1), 7-11.

[4] Pihlstrom, B. L., Michalowicz, B. S., & Johnson, N. W. (2005). Periodontal diseases.The Lancet, 366(9499), 1809-1820.

[5] Armitage, G. C. (1999). Development of a classification system for periodontal diseases and conditions.Annals of Periodontology, 4(1), 1-6.

[6] Papapanou, P. N., & Lindhe, J. (2003). Clinical Periodontology and Implant Dentistry (4th ed.). Blackwell Munksgaard.

[7] Albandar, J. M., Rams, T. E., & Slots, J. (1997). Disease progression in early-onset periodontitis.Journal of Periodontology, 68(10), 875-879.

[8] Borrell, L. N., & Papapanou, P. N. (2005). Periodontitis at a population level: trends and disparities.Journal of Clinical Periodontology, 32(10), 1045-1051.

[9] Genco, R. J., & Williams, P. L. (1998). Periodontal disease and diabetes: an overview of the evidence and implications for periodontal treatment.Compendium of Continuing Education in Dentistry, 19(11), 1145-1150.

[10] Sorsa, T., Tjäderhane, L., Konttinen, Y. T., et al. (2006). Collagenases in periodontal diseases.Annals of the New York Academy of Sciences, 1062(1), 312-321.

[11] Kornman, K. S., Crane, A., Wang, H. Y., et al. (1997). The interleukin-1 genotype as a risk factor for periodontal disease.Journal of Periodontal Research, 32(3), 329-331.