Genetic factors in pathogen colonisation is emerging as a new field of research as " infectogenomics". The susceptible host to periodontal disease directs towards genetic factors playing a role in periodontal disease pathogenesis. Earlier identification of gene polymorphisms associated with periodontal disease preogression may help in early diagnosis, treatment of such susceptible host.

1. PRESENTED BY- DR.OINAM MONICA DEVI

2. Loe et al (1986) in a longitudinal study of natural history of periodontitis
Variability of disease in population
This host susceptibility may be defined in terms of
“ GENETIC VARIATION ”
INTRODUCTION
Unrecognized components of
the environment
Differences among individuals in
their susceptibilities to disease

3. Albander
et al,2018

4. Complex Disease
Polygenic : multiple genes play each a limited role
Disease modifying genes : 10 to 20 for Periodontitis
Number & type Same condition
May not be equal for different forms of
periodontitis & different ethnic populations
Influenced by environmental factors
PERIODONTITIS

5. Human genome: > 3 billion base pairs
& 25000 to 30000 genes
OVERVIEW OF GENETICS

6. LOCI: Specific location on
chromosome
ALLELE: Variation in the
nucleotide sequence at a locus
(Polymorphisms)
TRAITS AND DISEASES
1. MONOGENIC
2. OLIGOGENIC
3. POLYGENIC
4. MULTIFACTORIAL

7. Individual genetic changes that are causal of disease are result of a genetic alteration
MUTATION
Dramatically alters a
protein’s function
 Rare in population
<0.1% of population
POLYMORPHISM
Minor change in function of a protein
More Common
Occurs at least 1% of population
Normal variant of population
POLYMORPHIC LOCUS
The most common, normal variant (N-allele) among them occurs with <99%
frequency in the population.
If a locus eg. bi-allelic, the rarer allele (designated R-allele) must occur with a
frequency >1% in the population.
When different alleles of a given gene co-exist in the human population, we
speak about genetic polymorphisms

8. Most common over any other type of polymorphism.
Represents a variation of one base in the DNA.
Create a unique DNA arrangement for individuals.
Frequency of SNPs across the human genome is estimated at every 0.3-1
kilobases
SINGLE NUCLEOTIDE POLYMORPHISMS

9. POLYMORPHISM ARISES AS A RESULT OF GENE MUTATIONS

10. GENETIC DISORDERS

11. Single Gene (Monogenic/ Mendelian) Disorders
Diseases that follow predictable and generally simple patterns of transmission
have been called Mendelian conditions.
Occur in simple patterns in families
Genetic alterations at a single gene locus are the major determinant of the
clinical disease phenotype referred to as causative gene.
Follow a classic Mendelian mode of inheritance.
 The population prevalence of individual Mendelian diseases is rare (typically
much less than 0.1%), with the exception of some unique populations

12. When the gene responsible for a Mendelian disease has been identified, it is
often possible to develop a diagnostic test to
1. Identify individuals who carry a disease-causing mutation
2. Determineof the probability of the mutant gene being passed to a child
3. Predict the course of clinical disease.
SYNDROMIC PERIODONTITIS

13. Non Mendelian Disorders/ Complex Diseases
Do not follow a simple pattern of familial transmission.
Result of the interaction of alleles at multiple different gene loci.
Environmental factors are usually etiologically important, and often necessary
On a population level, much more common with a prevalence of >1%.
The allelic variants are common in the population
 The individual genetic variants usually function within the normal range
Genes are often referred to as susceptibility genes / susceptibility alleles.
 The hypothesis that most of the genetic risk for common, complex diseases is due to
common polymorphisms at disease loci is known as the Common Disease⁄Common
Variant hypothesis.

14. Oro facial clefts Oral squamous cell carcinoma Periodontal disease
Knowledge of the presence of one disease-associated allele in an individual does
not provide enough information to make a clinical diagnosis.
NONSYNDROMIC PERIODONTITIS

15. GENETIC MARKER
 Refers to any gene or nucleotide sequence that can be mapped to a specific
location or region on a chromosome Eg: Blood groups, Protein isozymes, HLAs.
A person’s inherited variation directly at the DNA level can be determined for
much lower cost & with greater speed and accuracy with the next generation
DNA sequencing methods.
Whole genome arrays can evaluate up to 1 million variable DNA sites in a single
assay combined with lower-throughput methods used for fine mapping of
chromosome regions of special interest. These regions are said to contain
candidate genes of high priority for further investigation.

16. STUDY DESIGNS
FAMILIAL
AGGREGATION
SEGREGATION
ANALYSIS
TWIN
STUDIES
LINKAGE
STUDIES
ASSOCIATION
STUDIES

17. Familial Aggregation
 Familial aggregation of a trait or
disease can suggest genetic etiology.
 It may result from shared genes, shared
environmental exposures and similar
socioeconomic influences.
 There have been many clinical reports
suggesting a familial aggregation of
periodontitis, but until recently the
research tools to pursue these reports
were lacking.

18. Segregation Analysis
How Inherited diseases "run" in families.
Whether the disease alleles lie on autosomes or sex chromosomes, whether they
are dominant or recessive, and whether they are fully or partially penetrant.
Penetrance : probability that a particular phenotype will result from a
genotype.
Partially penetrant : only a fraction of individuals who inherit the disease
alleles will be affected.

19. AUTOSOMAL DOMINANT AUTOSOMAL RECESSIVE

20. The observed pattern of disease in families is compared with patterns
expected under various models of inheritance to select the best- fitting model.
The statistical power of this design depends on the number and composition
of the families and the heterogeneity of the disease.
LIMITATIONS:
1. Have low power to resolve heterogeneity.
2. Cannot distinguish between genetic effects and unmeasured
environmental causes of disease.

21.  In the classic twin study, reared-together monozygotic
(genetically identical) and dizygotic twins (fraternal
twins share on average 50% of their genes by descent)
are compared.
 For binary traits (present or absent) a genetic effect is
inferred if the positive concordance rate, or percentage
of twin pairs in which both twins are affected, is greater
for MZ than DZ twins.
 For continuous measures, such as periodontal probing
depth or attachment loss, intraclass correlations are
calculated. These correlations reflect the variation
between twin pairs relative to the variation within pairs
Twin Studies

22. Twin data are used to estimate heritability
 Very large samples of reared-together twins are needed to estimate heritability
with precision.
Heritability also can be estimated from MZ twins who are separated at birth
and raised apart.
REQUIREMENTS:
1. The disease has to be fairly common
2. Enough twin pairs available in which at least one of the twins is affected by
the disease
For periodontal diseases, only chronic periodontitis occurs frequently enough to
have been studied using the twin design.

23. LIMITATIONS:
1.Scarcity of such twins
2. Describe the impact of genes on specific populations exposed to a particular
range of environments.
3.Cannot be used to determine the mode of inheritance of a disorder or the
number or location of disease alleles.
(Michalowicz and colleagues, 1991)
Study group = 77 monozygotic twins (63 pairs were reared together and
14 were reared apart) and 33 dizygotic twins.
Relative contribution of environmental and host genetic factors to the
clinical factors of periodontal disease in adult twins.

24. Linkage And Association Studies
Linkage analysis is a technique used to localize the gene for a trait to a specific
chromosomal location
 Use sets of families, or pedigrees, with multiple affected individuals.
 Genotypes are determined for affected and unaffected family members.
 Complex statistical models are used to determine whether the marker
allele(s) and disease co-segregate in the families under a given inheritance
model.

25.  Logarithm of the odds (LOD) score: measure of the likelihood that the marker
and disease alleles are linked versus not linked at a given recombination rate.
 Linkage can be detected if the marker and disease alleles are within 20 to 30
centi Morgans (cM) of one another. ( 1cM = 1 million nucleotide bases)
 Typically conducted for qualitative traits or diseases.
 Successfully applied to syndromic forms of periodontitis.
 Has extremely low statistical power for complex diseases.
 The finding of true linkage disequilibrium implies that the disease and marker
alleles lie very close to one another on a chromosome and suggest that the
presence of an allele confers risk for disease within a defined environment

26. Genetic Association in Aggressive or Early
Onset-Periodontal Diseases:
The early onset periodontal diseases (EOP) are a group of diseases –
prepubertal, juvenile, and rapidly progressive periodontitis that occur in
children, adolescents, & young adults.
 The rate of periodontal destruction is greater in EOP .
 The immunologic and microbiologic profiles can vary substantially
within the subforms.
 This variability is due to both etiologic heterogeneity and genetic
heterogeneity.

27. Segregation Analysis of Early Onset Periodontitis
It has been recognized for years that juvenile periodontitis (JP) aggregates in
families.
African-
American,
Caucasian,
Asian
32(199) Autosomal
recessive
Tested autosomal recessive, X-
linked dominant and sporadic
models. X- linked dominant mode
favored in 8 of 33 kindreds
Long JC et
al (1987)
African-
American,
Caucasian
100 (631)
26 GJP
Autosomal
dominant
Disease dominant allele more
frequent in African-Americans than
Caucasians. 16 families with
cooccurrence of LJP and GJP
Marazita
ML et al
(1994)

28. • Schenkein HA et al (1994) proposed a model of inheritance that
distinguishes between the etiologies of localized and generalized EOP
and allows for family clustering
• Under this model, subjects with one EOP allele and two copies of the
high IgG2 response allele would develop only localized disease. In
contrast, subjects who carry the EOP allele and only one copy of the
IgG2 allele would develop more widespread disease because their
IgG2 response to LPS would be less robust.

29. Boughman JA et al(1986) : Autosomal dominant
Found cosegregation with dentinogenesis imperfecta (DGI). A putative JP
gene was localized to the long arm of chromosome 4 near the gene for
DGI.
Linkage Studies of Early Onset Periodontitis
Li Y et al (2004) Linked in 4 families with LAP to a marker on
chromosome 1 (1q25). The region containing putative
LAP locus spans over 25 million base pairs, and denser
marker sets or extensive sequencing will be needed to
narrow the region of interest.

30. Association Studies of Early Onset Periodontitis
Dyer JK et al,
1997
HLA-D antigens may mediate the association between
periodontal disease and IDDM.
Kaslick RS et al
1975, 1980,
Terasaki PI et
al 1975
Two antigens that appear to be consistently associated with
EOP are HLA-A9 and B15. The risk of disease in subjects
with HLA-A9 or B15 is about 1.5 to 3.5 times greater.
The HLA-A2 antigen appears to be less prevalent JP
suggesting that this antigen may be protective.

31. Genetic Association in Chronic (Adult) Periodontitis
Van der
Velden et
al (1993)
In young Indonesians
deprived of regular dental
care 23 family with 78
subjects aged 15-25 years
Showed a significant sibling
relationship effect for plaque,
calculus, and loss of attachment but
not for pocket depth.

32. Twin Studies of Adult Periodontitis
Michalowicz
BS et al
1991, 2000
110 and 117
pairs
Estimate heritability ranging between 40% to
80%
Moore WE et al,
1993
Adolescent twins have been found to be more similar in
their oral microbiota than pairs of unrelated individuals
Although host genes may influence initial colonization, this effect
does not persist into adulthood.

33. Association Studies of Adult Periodontitis
Goteiner D
et al (1984)
HLAB5 antigen was found to be more prevalent in adults
resistant to disease.
Kornman
KS et al
(1997)
“Composite" IL-1 genotype-consisting of at least one copy
of the more rare allele at both an IL-lα and IL-1β loci-was
associated with severe periodontitis in Northern European
adults. Nonsmokers with the composite genotype were 6.8
times more likely to have severe periodontal disease.

34. • Silva et al. demonstrated that the −889 C/T polymorphism was significantly
associated with a higher risk of chronic periodontitis.
• +3954 C/T polymorphism was associated with a higher risk of developing
chronic periodontitis in a metaanalysis based in Asian population
• One of the evidences that explain the association of polymorphisms in IL1B
only with chronic periodontitis is the fact that aggressive periodontitis is more
like a genetically inherited disease and the IL-1 gene is not related to the
specify genes.
• Association between periodontitis and polymorphisms in IL-4 was observed in
German, Brazilian, and Chinese patients
• Association between the IL-6 −572 G allele and chronic periodontitis in
Europeans
• IL-10 −819 gene polymorphism demonstrated association with chronic
periodontitis onset in Caucasian population

35. A given disease-modifying gene may not necessarily develop the disease; other
genetic risk factors (gene–gene interactions) &/ or environmental risk factors
(gene–environmental interactions) also need to be present simultaneously.
Disease-Modifying Genes in Relation to
Periodontitis
The disease-modifying genes contribute to susceptibility and severity of
periodontitis.

36.  A potent proinflammatory mediator
 Levels of IL-1α and IL-1β, (proinflammatory cytokines) and IL-1/IL-
receptor antagonist (RA, anti-inflammatory cytokine) ratio have been found
to be increased in diseased periodontal tissues and GCF.
Interleukin 1 (IL-1) Polymorphism
Following IL1 genetic polymorphisms have been studied in relation to
periodontitis:
IL1A-889 (in linkage with +4845),
IL1B-511 (in linkage with-31),
IL1B +3954 (also mentioned in the literature as +3953) and
IL1RN VNTR (in linkage with +2018).
Kornman et al. (1997) reported first on polymorphisms for the IL1 genes in
relation to periodontitis.

37. A proinflammatory cytokine
TNFA gene is located on chromosome 6p21.3 within the MHC gene
cluster.
Putative risk factors for periodontitis
 SNPs in the TNF-α are : in the promoter region at positions -1031, -863, -67,
-308, -238 in the coding region in the first intron at position +489.
Tumor Necrosis Factor- α (TNF-α) Gene
Polymorphism

38. Galbraith et al.
(1998)
Among Caucasians, the only association of a TNFA
polymorphism was observed at position -308
Kornman et al.
1997;
Galbraith et al.
1998
Lack of association of TNFA genetic polymorphisms with
the severity of periodontitis

39. Leukocytes from both the myeloid and lymphoid lineages express receptors (FcγR) for
the constant (Fc) region of immunoglobulin G molecules.
Microorganisms and bacterial antigens, opsonized with antibody, can be
phagocytosed via FcγR on neutrophils or internalized via FcγR by a variety of
antigen-presenting cells (APCs).
Fcɣ R gene polymorphisms
Meisel et al. 2001;
Loos et al. 2003
For the FcγRIIIa gene again a lower R-allele carriage
rate is seen in Japanese than in Caucasian and African
American subjects.
The FcγRIIIa N-allele (V158) seems as a putative risk
factor for periodontitis
In Japan, both the FcγRIIIa R-allele (F158), as well as
the FcγRIIIa N-allele, were proposed as risk factors.

40. First line of defense in infectious diseases.
Recognizes pathogen-associated molecular
patterns (PAMPs) expressed on
microorganisms.
 Extra- and intracellular receptors like CD14,
CARD15, and TLRs recognize PAMPs of
Gram-+ve & Gram –ve bacteria.

 Mediate the production of cytokines necessary
for further development of effective immune
response.
Gene polymorphisms in the innate immunity receptors

41. CD14
Located on chromosome
5q21–q23.
CD14 –260 N-allele leads to a reduced
expression of the CD14 receptor it is
assumed that individuals carrying the N-
allele may be more susceptible to CP.
8 studies have investigated the CD14-260 polymorphism in Caucasian CP
subjects:
2 studies found an association with the N-allele (Folwaczny et al 2004,
Donati et al 2005) and another study with the R-allele (Laine et al 2005)
5 studies did not find any association with the CP susceptibility [Holla et al
2002, James et al 2007, Schulz et al 2008, Nicu et al 2009, Yamazaki et al
2003].

42. TLRs
TLR 2 and TLR4 genes map on chromosome 4q32 and 9q32-
q33, respectively.
TLR2 Arg677Trp and Arg753Gln gene polymorphisms have
been reported to change the ability of TLR2 to mediate a
response to bacterial components .
Two common cosegregating missense polymorphisms of TLR4,
Asp299Gly and Thr399Ile, leading to an attenuated efficacy of LPS
signalling and a reduced capacity to elicit inflammation.

43. Nine SNPs in the TLR 2 and TLR4 genes have been studied by
Fukusaki et al. [2007] in a Japanese population, and TLR4 +3725
polymorphism was found to be associated with CP.
TLR2 677 loci was not polymorphic in Caucasian and Japanese
populations [Berdeli et al 2007, Fukusaki et al. 2007], but the
heterozygotic genotype was found in 100% of the Han Chinese [Zhu
et al 2008].
The TLR2 753 and the TLR4 polymorphisms were not or in very low
percentage polymorphic in Asian populations.

44. CARD
Folwaczny et al.
2004c; Laine et al.
2004
Polymorphisms of the CARD15 (NOD2) gene have
not been associated with periodontitis

45. Vitamin D receptor gene polymorphisms
Hennig et al. 1999; Tachi
et al. 2001; Yoshihara et
al. 2001; Sun et al. 2002;
de Brito Junior et al.
2004
Tachi et al. 2003
In five case–control studies an association of the
R-allele with several forms of periodontitis have
been observed
In Japanese study an association with the N-
allele has been found

46. IL-10 gene polymorphisms
 Anti-inflammatory cytokine.
 Can stimulate the generation of auto-antibodies.
 Located on chromosome 1, in a cluster with closely related interleukin
genes, including IL19, IL20, & IL24.
 Produced by monocytes/macrophages and T cells and plays a role in the
regulation of pro-inflammatory cytokines such as IL-1 and TNF-α.
Scarel-
Caminaga et al.
2004
In Brazilian study observed a trend for increased carriage of
the IL10 -1087 N-allele among controls.

47. Polymorphisms in the IL4 and IL4RA Genes
• IL-4: pleiotropic cytokine, Located on chromosome 5q31.1.
• PromotesB-lymphocyte mediated immunity.
• Downregulates macrophage function.
• An IL4 -590 promoter polymorphism and a 70-bp VNTR
polymorphism are the most studied polymorphisms of IL4.
Holla et al,
2008
Case–control studies have not shown any relationship between
the IL4 gene polymorphims and susceptibility to chronic
periodontitis (CP) in several different populations.
A haplotype of IL4 polymorphisms (carriers of R-alleles) has
been associated with CP.

48. Polymorphisms in the IL6 and IL6R Genes
Localized on chromosome 7p21.
The -174 was found to influence IL-6 expression and production.
The -174 R-allele carrier individuals have decreased plasma levels of IL-6
& present lower IL6 gene transcriptional activity.
 Genetically determined low IL-6 response (the -174 R-allele
carriers) may hamper individual’s defense against periodontal pathogens.

49.  Adavances in genetics is seen since 1990 with the beginning of Human
Genome Project .
 GWAS investigates genetic variation across the entire genome
simultaneously, with the aim of identifying genetic associations related to a
trait or disease of interest.
 GWAS has the potential to identify the genetic contributions to common
diseases.
 The entire Genome is analyzed.
Genetic and Genomic Methods of the 21st
Century
Genome Wide Association Studies (GWAS)

50.  1st wave of GWAS (2007–2010) : Genetic gold rush of human genetics,
many of the common genetic risk factors of complex human diseases were
identified.
 GWAS present an efficient way of screening for genetic polymorphisms
associated with diseases.
 GWAS provide an unbiased and hypothesis‐free approach.
 The current standard of declaring statistical significance at a genome-
wide level is a combined p- value of p < 5 ×10₋8
 The disadvantage is it requires large clinical sample sizes.

55. GENE Function
ANRIL(antisense non‐coding RNA in
the INK4 locus)
Has a negative regulatory effect on the
expression of the adjacent
cycline‐dependent kinase inhibitor genes
CDKN2A and CDKN2B (Yap et al.
2010)
CAMTA1/VAMP3(calmodulin‐binding
transcription activator 1/vesicle
‐associated membrane protein 3)
VAMP3 plays a role in phagocytosis,
mediates delivery of tumor necrosis
factor‐alpha (TNF‐α) to the cell surface
GWAS on periodontal pathogen
colonization, a large stretch of the
CAMTA1/VAMP3 region was reported to
be strongly associated with increased
quantities of pathogenic oral bacteria
(Divaris et al. 2012).
GLT6D1(glycosyltransferase domain‐1) Risk gene of aggressive
periodontitis((Schafer et al. 2010)

56. COX‐2 COX‐2 converts arachidonic acid into
prostaglandin H2
NPY(neuropeptide Y) Alter the pro‐inflammatory T‐helper
type 1 (Th1)‐to‐anti‐inflammatory
T‐helper type 2 (Th2) balance
The genes ANRIL, GLT6D1, COX‐2, and NPY are conclusive risk genes of
periodontitis, (ANRIL, COX‐2, and NPY for both aggressive and chronic
periodontitis; GLT6D1 for aggressive periodontitis only)

58.  “Epigenetics” was coined by Conrad Waddington
 Greek prefix ‘epi-’ means ‘on the top of’ or ‘in addition to’ genetics.
 Epigenetics is the study of stable genetic modifications that result in
changes in gene expression and function without a corresponding alteration
in DNA sequence.
EPIGENETICS
EPIGENETIC CODE
(cumulative alterations)
Structural organization of
chromatin on different
hierarchal levels

59. “Epigenome” literally meaning “beyond the genome“.
It is defined as the study of mitotically and meiotically heritable changes in
gene function that are not dependent on DNA sequence.
Inherited Genome Environmental
influence
EPIGENOME
( Chromatin &
its
modifications)
Homeostatic profile of
gene expression

60. Epigenetic modifications include chemical alterations of DNA and associated
proteins, leading to remodeling of the chromatin and activation or inactivation
of a gene.
 Epigenetic modifications are potentially reversible and transient.
 Many environmental factors affect these mechanisms.
PERIODONTITIS
Susceptibility
genes/ Alleles
Individuals with such genes
develop disease ONLY when
exposed to DELETERIOUS
ENVIRONMENT
1) Gram negative anaerobic
microorganisms
2) Cigarette smoking
3) Poor oral hygiene

61. A potential hypothesis of the epigenetic events occurring in a CP lesion (Larsson L et al, 2015)

63. Major Epigenetic Mechanism that regulate Transcriptional action
DNA
METHYLATION
POST-
TRANSLATIONAL
MODIFICATION OF
HISTONES
NONCODING
RNAs
NUCLEOSOME
REMODELERS
HISTONE H3
VARIANTS

64. SAM: S adenosyl Methionine
DNA Methyl transferase
Gene silencing
Exposed methyl group – interact with methyl binding proteins – chromatin condensatin
Changes of DNA methylation patterns and cytokine gene expression can
be observed in chronic periodontitis.
( Lindroth AM 2013, Zhang S 2010, 2013)

65. Histone modifications may induce differentiation and mineralization in
dental pulp stem cells*
Duncan HF, Smith AJ, Fleming GJ, Cooper PR. Histone deacetylase inhibitors epigenetically promote reparative
events in primary dental pulp cells. Exp Cell Res 2013; 319:1534-43.

66. Functionally relevant RNA molecules, despite not encoding for a protein.
Transfer RNAs (tRNAs),
Ribosomal RNAs (rRNAs),
MicroRNAs (miRNAs), and
Short-interfering RNAs (siRNAs)
miRNAs and siRNAs, have been shown to regulate gene expression without
altering the DNA sequence
• Studies have reported that non-coding RNAs are involved in oral diseases such as
specific syndromes, oral cancer and oral immunology.
• Studies have demonstrated that miRNAs play essential roles in odontoblast
differentiation. (Sun Q 2014, Perez P 2014)

67.  Stimulate transcription by detaching nucleosomes from promoter regions of genes
Mammalian cells express: H3.1, H3.2, and H3.3
 Specific enrichment of H3.3 in active and regulatory regions
 H3.1 in inactive genetic elements
Direct methylation of histones can result in gene silencing or activation

68. Grover et al, 2014

69. IL-8
promoter
Andia DC et al , 2010 reported Hypomethylated in oral epithelial
cells from individuals with generalized AgP compared with
healthy controls.
IFN-γ,
IL-10
Viana et al. (2011) reported a similar methylation level of IFN-γ
and IL-10 in gingival biopsies from patients with CP

70. Stimulation with
Treponema
denticola
Decrease in methylation of the MMP-2 promoter.
.( Miao D, 2014)
P. gingivalis The culture supernatant from P. gingivalis containing
high levels of butyric acid reported to inhibit histone
deacetylases (HDACs,) resulting in increased histone
acetylation. (Imai K, 2009, 2012)

71.  Infectogenomics was first defined by Kellam & Weiss (2006) as the study of
interaction between host genetic variations and colonisation by pathogenic
microbes.
No specific single gene polymorphism could be defined,owing to
polygenic nature of Periodontal disease.
The concept for infectogenomics states that the geneticd efects in the
recognition & response pathways of the host to identify microbial pathogens
predispose to either altered microbial colonisation or misrecognition of
normalmicrobiota leading to dysbiosis and appearance of infectious disease.

72. Role of Infectogenetics in Periodontal pathogenesis:
1.Genetic factors can affect periodontal pathogen invasion
2. Genetic factors can affectperiodontal pathogen
proliferation/ clearance
The concept of periodontal infectogenomics has been investigated
in GWAS in addition to cross sectional or case control study designs.
Among participants of the Atherosclerosis Risk in
Communities (ARIC, 1989) longitudinal cohort investigation ,
1. No significant genome wide signals
2. 13 loci, including KCNK1, FBXO38, UHRF2, IL33, RUNX2, TRPS1,
CAMTA1, and VAMP3, provide an evidence of association for red & orange
complex microbiota except Aggregatibacter actinomycetemcomitans.

73. Recently genome wide association of chronic periodontitis is conducted by supplementing clinical data with
biological intermediates of microbial burden and local inflammatory response with the formation of
periodontal complex traits (PCTs).

74. Gene Associated micro organisms
IL-6 hyperproducers Consistent association with Aggregatibacter
actinomycetemcomitans
IL-1 and TNF-α polymorphisms Subgingival colonisation of red and orange
complex bacteria
IL-4, IL-8 and IL-10 polymorphisms Associated with microbial colonisation
vis IL-2, IL-12, IFN-γ, HLA class II, NF-κβ,
vitamin D receptor, MMP- 8, T-bet,
apolipoprotein E and PPARγ polymorphisms
No significant association with the pathogen
colonisation
IL-2, IFN-γ, HLA class II and NF-κβ
genotype
Needs further exploration of this association.
pathogen detection receptors viz. CD14 260
CT + TT genotype
Association with the red complex bacterias.
MBL2 homozygote variant Virulence of A. actinomycetemcomitans
CD14 260 and IL-10 haplotype Red complex bacteria

75. • Genome Wide Association Studies and next generation DNA sequencing
techniques
• Strategy of individualized medicine
• Improved evidence-based practices for periodontal disease prevention,
diagnosis, and treatment
• New interdisciplinary teams with dentists as key members working with
experts in bioinformatics, genomics, and genetic counseling.
 In dentistry, a test based on genetic variation at IL-1α and IL-1β cytokine
and receptor antagonist genes to predict progression and severity of
periodontitis has been commercialized and is still offered today, although it
does not appear to be widely used.

76. 1. Role of host genes in the etiology and pathogenesis of the periodontal
diseases.
2. Genetic test will be useful as screening tool in only a subset of patients or
populations.
3. Knowledge of specific genetic risk factors enable clinicians to direct
environmentally based prevention and treatments to individuals who are
most susceptible to disease.
4. Useful in predicting treatment outcomes.
5. Recognizing and controlling important environmental risk factors.
6. New treatment strategies will be developed to directly counter the
deleterious effects of certain risk allele(s).

77. 1. The classification of disease used for research studies
2. In Family studies the handling of parents, siblings, and other close relatives who may be
neither clearly periodontally healthy nor clearly diseased is not easy to decide.
3. Aspect of the diagnosis challenge that is how and why different teeth are affected by
periodontitis. One way to begin to address the problem of variation among teeth is to apply
multivariate methods.
4. Even GWAS studies have failed to identify most of the genetic variation responsible for the
disease.
5. Sequencing methods combined with the proteomic assays, will challenge investigators with
huge quantities of information.
6. In developing the bioinformatics tools to shift through and identify the key bits of information
important for advancing our knowledge.

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80. Thank you