Genetics and periodontal disease Patients with periodontitis show inflammatory destruction of the supporting tissues around the teeth. Loss of connective tissue and collagen in the gingiva is characteristic, along with loss of periodontal ligament and resorption of alveolar bone. Thus the tooth roots become exposed to the oral environment, and the root and root cementum are colonized with a bacterial biofilm, which can calcify to form dental calculus. The chronicity and mostly slow progression of this disease results in tooth mobility, loss of chewing function, esthetic disturbances and, ultimately, if left untreated, tooth exfoliation. Moreover, periodontal inflammation has systemic effects; it can induce low grade systemic inflammation, which has negative effects on other organs. Periodontitis is a complex chronic inflammatory disease with nonlinear progression that is caused by various factors each playing a role simultaneously and interacting with each other. The various factors determine the immune fitness of a subject. The host exists in a symbiotic relationship with the oral microbiome to maintain homeostasis. Loss of homeostasis results from loss of the host balance and an aberrant host response. This aberrant host response can manifest as a hyper‐ or hyporesponsiveness and/or lack of sufficient resolution of inflammatory reactions. The consequent chronic inflammation elicits changes in the ecology of the subgingival environment providing favorable conditions for the overgrowth of pathobionts that further propagate periodontal inflammation. The factors that determine immune fitness include: (a) genetic factors and epigenetic factors; (b) lifestyle factors; (c) comorbidities; (d) local or dental factors and factors that act randomly; and (e) pathobionts in a dysbiotic subgingival biofilm. Variants in at least 65 genes to date have been suggested as being associated with periodontitis based on genome‐wide association studies and candidate gene case control studies. Interestingly, reports have found pleiotropy between periodontitis and cardiovascular diseases. To date, 4 genetic loci are shared between coronary artery disease and periodontitis. The shared genes suggest that periodontitis is not causally related to atherosclerotic diseases, but rather both conditions are sequelae of similar (the same?) aberrant inflammatory pathways. In addition to variations in genomic sequences, epigenetic modifications of DNA can affect the genetic blueprint of the host responses.

1. ROLL NO. 02
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2. Introduction
Insight To Genetics
Genetic Study Designs
Genetic Basis Of Periodontitis
Evidence For The Role Of Genetic
Variants In Periodontitis
Genetic Syndromes Associated With
Periodontitis
Gene Therapy
Clinical Utility Of Genetics In Periodontics
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3. o Genetics is the study and understanding of
the phenomena of heredity and variation.
o A large number of genes are associated with
many systemic conditions.
o Genetic factors impair inflammatory and
immune responses in an individual.
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4. •Periodontitis is inflammatory condition and genetic
factors play a role in its etiology.
•Genetic factors play a role in the predisposition and
progression of periodontal diseases.
•Periodontal diseases occur due to complex interplay
between Environmental factors, Genetic factors,
Life style factors, Systemic diseases and other
factors.
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5. Genetic multi-causality model for periodontitis
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6. •Genetic risk factors like gene–gene interactions,
gene-environmental, and environment–gene-life
style interaction need to be present
simultaneously for the phenotype to develop in
periodontal disease.
•The study of the role of genetic factors in
determining health and disease in families and in
populations, and the interplay of
such genetic factors with environmental factors is
known as Genetic Epidemiology.
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7.  Gene- a functional and physical unit of inheritance
that occupies a specific position (locus) within
chromosome.
 Chromosome- a nuclear structure carrying genetic
information arranged in a linear sequence.
 Genome - refers to all the genes carried by an
individual or cell.
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8. Allele– one of several
possible alternative forms
of a given gene at a
particular locus of a
chromosome differing in
DNA sequence.
Homozygous – the presence of identical alleles
of one or more specific genes (e.g. A/A).
Heterozygous – the presence of differing alleles
of one or more specific genes (e.g. A/B).
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9. Genotype- genetic makeup of an organism.
Phenotype- observable characteristics displayed by
an organism as influenced by environmental factors.
Genetic marker- Any nucleotide sequence on a
particular locus that is used to map or locate the
disease allele.
Autosomal dominant- A gene that shows its effect
regardless of the presence of the other normal copy.
Autosomal recessive- A gene that is required in two
copies to be active in an individual.
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10. Mutation- a permanent transmissible change in the
genetic material that occur during DNA replication or
meiosis. (<1% of population)
Polymorphism- a region on the genome that varies
between individual members of a population. (>1% of
population). Occurs due to mutation.
1. Single nucleotide polymorphism (SNP): simplest
type & results from a single base mutation.
Frequency : 0.3–1 kb
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11. 2. Restriction Fragment length polymorphism (RFLP)
Digestion of a piece of DNA containing the relevant site
with an appropriate restriction enzyme could then
distinguish alleles or variants based on the resulting
fragment sizes via electrophoresis.
3. Insertion-deletion polymorphism
Results from insertion or deletion of a section of DNA.
Most common type is existence of variable numbers of
repeated base or nucleotide patterns in a genetic region
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12. 1. SEGREGATION ANALYSIS
o Used to study the inheritance of disease among
the families.
o Pattern of transmission depends on
 whether the alleles are dominant and recessive
 whether they are contained in autosomes or sex
chromosomes.
 whether they are partially or fully penetrant.
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13. o Dominant allele always determines the
phenotype.
o Recessive allele is inherited only when it is
present at both loci on homologous
chromosomes.
o Power of segregation analysis is dependant
upon the size of population to study the
observed pattern of disease.
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14. Drawbacks
 Mode of inheritance among older individual
was difficult to carry out.
 Relation b/w environmental and genetic
heterogenecity not explained.
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15. 2. Twin Studies
oUsed to study the influence of genetic and
environmental factors on the complex diseases
like periodontitis with multifactorial etiology.
oCovers the drawbacks of segregation analysis.
oThe subject of interest in twin studies can be
monozygotic or dizygotic twins.
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16. oTwin studies are used to estimate the
inheritance of phenotypic variations among
twins that are reared apart or together.
oAny similarities b/w both of them will be
attributed to their shared genes and
dissimilarities will be because of environmental
factors.
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17. 3. Linkage and Association Analysis
o Used to map disease allele to specific regions on
chromosomes
o Probability of recombination of two allele at
different loci is proportional to the distance
b/w them.
o By identifying the genetic markers associated
with the disease causing alleles the researchers
can alter the location of disease allele.
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18. o Marker and disease allele are used to
determine the inheritance of disease within
families.
oGenerally the inheritance of a disease can be
established if the distance b/w marker and ds.
Allele is within 20-30 centimorgan (cM).
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19. oLinkage disequilibrium- when same marker allele is
associated with disease in multiple families.
oTo test this association the frequency of allele at
a given locus is compared in subjects with disease
and healthy controls.
oTrue linkage disequilibrium means marker and
disease allele lie close to each other on
chromosomes and the chances of disease are more.
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20. oThe association b/w marker and disease allele
may not due to genetic origin or environmental
influence.
oIn the presence of particular pathogens the
individuals with low responsive alleles will develop
disease and if no pathogen are present then no
relationship exist b/w the two.
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21. 4. Genome-wide Association Study (GWAS)
oPowerful molecular technique to analyse variations
in genomic DNA and determine if any genetic locus
is associated with a certain disease phenotype.
oGWAS has an open-ended approach & analyses
SNPs covering the entire human genome
oIt enables the investigation of possible roles in
biological pathways, especially in diseases such as
periodontitis
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22.  Periodontitis is a complex chronic inflammatory
disease which affects gingiva, periodontal
ligament, cementum, and alveolar bone.
 Periodontitis is classified into Chronic
Periodontitis (CP) and Aggressive
Periodontitis(AgP).
 AgP occurs most often at a younger age (upto
35 years old) and these cases involve more
genetic risk factors than CP cases
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23. Genetic contribution to the aetiology of periodontitis
23

24. o The evidence for a genetic predisposition to
aggressive periodontitis comes from
segregation analyses of families with affected
individuals in two or more generations.
o It inherited in a Mendelian manner, and both
autosomal modes and X-linked transmission have
been proposed.
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25. GENES ASSOCIATED WITH AGGRESSIVE PERIODONTITIS
• IL-1 cluster, IL-4,6,10,12,13,18
• TNF-a
• TGF-b
• Vit. D receptor
• Estrogen receptor
• RANK/RANKL/OPG,
• MMP 1,2,3,9,
• TIMP
• HLA
• CD14
• Cathepsin C, IFN-gamma.
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26. o In contrast to aggressive periodontitis, chronic
periodontitis does not typically follow a simple
pattern of familial transmission or distribution.
o The twin study is most popular method that supports
the genetic aspects of chronic periodontitis.
Corey et al. (1993)
revealed that approximately half of the variance in
disease in the population is attributed to genetic
variance. 26

27. Michalowicz et al. (1991)
•The rate of occurrence of periodontitis was more in
monozygotic twins (23%) as compared to Dizygotic twins
( 8%).
•These studies are independent of environmental factors
showing that gene control only the biologic mode of
inheritance and not the behavioral.
GENES ASSOCIATED WITH CHRONIC PERIODONTITIS
• Interleukin-1, 2, 4, 6, 10
• Fcg receptor
• TNF
• Vitamin D receptor
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28. Familial Aggregation:
German studies of familial nature in the early 20th
century have shown aggregation of chronic
forms of periodontitis in families. This
strongly suggested genetic predisposition.
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29. Twin study
oMichalowicz et al. (1991) studied dizygous twins reared
together and apart and monozygous twins reared together
and apart.
oMean probing depth and attachment level varied less for
monozygous twins than dizygous twins.
oTwin groups had similar oral hygiene and smoking history.
oConcluded genetics plays a role in susceptibility to
periodontal disease.
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30. Segregation analysis
• Marazita et al. (1994) studied >100 families,
segregating aggressive forms of periodontitis, and
found support for autosomal dominant transmission.
Concluded autosomal dominant inheritance with ~70%
penetrance occurred in Blacks and non-Blacks.
• While others Beaty et al. (1987), Long et al. (1987),
Saxen et al. (1980) have found support for autosomal
recessive transmission of aggressive periodontitis.
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31. Linkage analysis
1. Boughman et al. (1986) gene for Dentinogenesis
imperfecta-III had been previously localized to
chromosome 4. They showed close linkage of gene for
Aggressive periodontitis( AgP) to this DGI-III gene.
2. Hart et al. (1993) evaluated support for linkage of AgP
near chromosome 4 in different population of families.
Results showed that in these populations no linkage existed.
3. Li and co-workers (2004) reported evidence of a gene
responsible for localized aggressive periodontitis located on
chromosome 1q25.
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32. 32

33. o Autosomal recessive
disorder
o Characterized by
Cutaneous and Oral
manifestations.
o Skin lesions consist of
keratotic lesions of
palmar and planter
surfaces.
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34. oOral lesions are characterized by Aggressive
periodontitis leading to severe destruction of alveolar
bone, which leads to mobility, pathological migration and
loss of teeth.
oGene responsible: Cathepsin C, Lysosomal protease.
34

35. o Genetic defect in collagen and connective tissue
synthesis and structure.
o Characterized by joint hypermobility,
cutaneous fragility and hyperextensibility.
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36. oHyperelasticity of joints along with
defect in collagen causing more periodontal
destruction.
oEDS can be associated with Ligneous
periodontitis (gen. membranous gingival
enlargement due to accumulation of fibrin
deposits associated with severe bone loss).
36

37. oGingival tissue appear fragile and bleed after tooth
brushing, gingival hyperplasia and fibrous nodules also
noted.
oHypermobility of temporomandibular joint often results
in dislocation of jaw.
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38. o Autosomal recessive immunodeficiency disorder
characterized by abnormal intracellular protein
transport.
o Severe gingivitis and rapid loss of attachment,
leading to exfoliation of the teeth is seen.
oPeriodontal breakdown
occurs due to defective
leukocyte function.
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39. o It is of two types: LAD I and LAD II
o Autosomal recessive disorder, occurs by
mutation in the gene encoding for CD 18 integrin
(LAD I) and CD 15 integrin (LAD II).
o The defective or absent expression of these
molecules on the surface of leukocytes
decreases their ability to adhere to endothelial
cells and to migrate to sites of infection.
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40. oClinical features usually present in infancy consist
of recurrent, indolent bacterial infections of the
skin, mouth, & the respiratory tract.
oSevere gingivitis with an early loss of primary
teeth, followed by the early loss of secondary
teeth, is seen.
oSevere form of periodontitis is seen that does not
require specific periodontal pathogens because of
entrapment of neutrophils within the blood vessel.
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41. o Trisomy of chromosome 21
o Periodontal disease in Down syndrome is
characterized by formation of deep
pockets associated with plaque
accumulation and moderate gingivitis.
o This is due to;
− a reduced resistance to infections
− a defect in T-cell maturation and
polymorphonuclear leukocyte chemotaxis.
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42. o Both autosomal dominant and recessive
inheritance
o Associated with mutation in alkaline
Phosphatase gene ( Ip36. Ip34).
o Includes cemental hypoplasia, aggressive
periodontitis, premature loss of 1º and 2º
teeth.
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43. o Use of purified preparations of a gene or a fraction
of a gene, to treat diseases.
o There are four approaches:
a. A normal gene inserted to compensate for a
nonfunctional gene.
b. An abnormal gene swapped for a normal gene.
c. An abnormal gene repaired through selective
reverse mutation.
d. Change the regulation of gene pairs.
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44. 1. Protein based approach
2. Cell based approach
3. Gene- delivery approach
-In vivo gene Delivery
-Ex vivo gene delivery
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45. • Role of host gene in the etiology and
pathogenesis of the periodontal disease is
just begun to be understood.
• Association between polymorphisms in IL-1
genes and severity of periodontitis has been
described as a major breakthrough in clinical
practice.
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46. o The clinical test for such a genetic risk has been
proposed as a component of the risk assessment
profile for chronic periodontitis that can be used
to provide a rationale for explaining individual
patient susceptibility, providing early preventive or
therapeutic intervention, and allowing superior
prognostic capabilities.
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