The document discusses the role of genetics as a risk factor for periodontal disease, highlighting various genetic polymorphisms and their associations with chronic and aggressive periodontitis. It details different methodologies for genetic studies, such as segregation analysis, linkage analysis, and association studies, and emphasizes the significance of specific cytokine gene polymorphisms in the disease's progression. The document also presents numerous examples of genetic factors that contribute to periodontal disease susceptibility and the complexities of genetic versus environmental influences.

1. Genetics as a risk factor for
Periodontal disease
Dr.Sheeja S.Varghese
Professor: Saveetha Dental College

2. Periodontitis – A Multi Factorial Disease
Microbial Factors
Environmental Factors
Tooth factors
Systemic Factors
Behavioral Factors
Genetic Factors
Periodontitis

3. Types of Causation
1.Sufficient Cause
In the presence of which, the disease will always occur.
Example: genetic anomalies
2.Necessary Cause
It must be present for a disease to manifest (but presence does not necessarily
result in manifestation of disease).
Example: Tuberculosis
3.Risk factor
It has an association to a particular disease.
Relationship is not necessary causal in nature.
a. Risk factor - confirmed by longitudinal & cross sectional study.
b. Risk determinant - Non modifiable risk factor.
c. Risk indicator - confirmed only by cross sectional study.
d. Risk marker - Predict future course

4. Is Genetics a Causative factor or risk factor for
Chronic Periodontitis
Aggressive Periodontitis
Periodontitis as a manifestation of Systemic Disease
?

5. Why Genetics is linked to Periodontitis ?
Environmental & microbial factor cannot always
explain
1. Variations in the disease susceptibility
Loe et al (1986) – SriLankan tea workers
- 8% Rapid progression
- 81% moderate progression
- 11% no progression
Velden etal – (2006)- Westernjavapopulation -
20% severe destruction.
2. Familial aggregation & Heritability

6. Basics about human genes
23 Pairs of Chromosomes
22 pairs autosomal chromosomes
1 pair sex chromosomes
Each Chromose contains long
duplex of DNA.
Building blocks of DNA are
nucleotides(adenine(A),guanine(G),
cytosine(C) and thymine(T) linked to
deoxy ribose and PO4.Double helix of
DNA in formed by hydrogen bonding
between complimentary pairs(A-T&
G-C)

7. Gene - Heriditary unit that occupies a specific
position(Locus) within a genome or chromosome that
has one or more specific effects upon the phenotype of
organism
Gene expression - the process involving use of the
information in a gene via transcription and translation
leading to production of a protein affecting the
phenotype of the organism determined by that gene.
Genetic code - the consecutive nucleotide
triplets(Codon) in DNA or RNA that specify the
sequence of amino acids for protein synthesis.

8. Gene – Consists of two Parts
1. Coding region - Reading frame starting at
nucleotide Position +1 containing triplets or codon.
Consist of Exons - true coding region
&
Introns - non coding region
2. Promoter region - sequence of nucleotide left
(upstream) of the coding region
starting with nucleotide position -1(not as triplets)

10. A Region on the genome that varies between
individual members of a population present in a
significant numbers of individuals(more than1%)
Variant forms of a gene are called alleles.
Most common or Normal variant - N - allele
Rarer allele - R -
allele
Polymorphism are due to gene mutation
Genetic Polymorphism

11. Types
1.Minisatellite Variable Number Tandem Repeat(VNTR)Polymorphism.
- highly polymorphic
- not evenly dispersed (usually in telomeres)
2. Microsatellite Polymorphisms
- Short sequence of 1 – 4 bases
- Highly polymorphic
- more evenly distributed
- more numerous than mini satellite.
- but not very popular on genetic marker as their
frequency is only one in every 3 -10 kb in the genome.

12. 3. Single Nucleotide Polymorphism - Variation
in single base pair
- mutation rate of SNP is very low from generation to generation
- Very numerous (every 0.3 – 1kb)
- Easily detectable with PCR
1.42 million SNPs are there in human genome and around 60,000
are in the exones
SNPs are as a result of
1.Insertion
2.Deletion
3.Substitution
Example: ABO antigens

13. ABO antigens
CGT GGT GAC CCC TT
A-antigen sequence
substitution Deletion of G
(4 base pairs) (single)
CGT CGT CAC CGC TA CGT GGT ACC CCT T
B-antigen sequence O-antigen sequence

14. Can polymorphism influence the phenotype ?
1. Can be non functional
2. Can be functional
Coding region - may change the amino acid
thus can alter the protein.
Promoter or enhancer region –Increase or
decrease the amount of protein.

15. Genetic Study Designs
1. Segregation analysis
Pattern of transmission of disease
through generation is studied in different
families. It is compared with those
expected under various models of
inheritance to select the best fitting
model.
Adv: Can assess whether the disease gene is
autosomal or sexlinked, recessive or
dominant.
Limitation: It has low power to resolve
heterogeneity (Multiple causes)
Cannot distinguish between genetic &
environmental influences.
Does not provide information about specific genes

17. Twin Studies
Adv : The relative influence of genetic
and environmental factors on
complex diseases can be
estimated.
Two Types:
1. Classic twin study -
Reared together monozygotic and
dizygotic twins are compared.
2.Comparison of reared together and raised apart
monozygotic twins.

18. Linkage Analysis
 Used to map disease allele to specific regions on the chromosomes.
 Linkage -the tendency for certain genes to be inherited together
due to their close presence on the same chromosome. By
indentifying genetic marker that segregate with a disease,
the location of the disease allele can be inferred.
 LOD(Logaritham of odds) score - Compare the likely hood of two
genes are indeed linked to the likely hood of observing
this data purely by chance.
+ve LOD score- presence of linkage
-ve LOD score-less likely
 Linkage disequilibrium – the occurrence of some genes together
more often than would be expected by random distribution

19. Crossing over in meiosis

20. Association Studies
 Frequency of alleles at a given locus is compared
between subjects with disease(cases) and healthy
controls sampled from same population .
 Limitation – Association does not necessarily
imply a biologic link between the disease and the tested
allele.

21. Evidences for genetics as risk
factor

22. Twin Studies
 Observations:
• Periodontal condition of identical twins were similar (Noak- 1940)
• Monozygotic twins were more similar than dizygotic
twins for clinical parameter of chronic Periodontitis
(50% heritability)
• Gingivitis did not have heritability component
• Reared apart MZ twins were no less similar than reared together MZ twins
in their Periodontal status.
• The twin study is probably the most popular method that support the
genetic aspects of chronic Periodontitis.

23. Segregation analysis
Chronic Periodontitis does not follow familial
transmission.
Various authors suggested different modes of
inheritance for aggressive Peridontitis.
Majority of Studies - autosomal recessive
A few studies - autosomal dominant
-X-linked dominant

24. Linkage Studies
• Linkage between AP with dentinogenesis
imperfecta (Boughman etal 1986)
• The putative AP disease gene was localized to
chromosome 4q11 – 13
• But Hart in 1993 reported that AP disease gene
resides with in this chromosonal region is
highly unlikely.
• Li et al 2004 linked LAP to a markers on
chromosome 1(1q25) in 4 families (LOD
score 3.48)

25. Association Studies
Utilizes candidate geneapproach for polymorphism studies
- Tries to identify one allele of a gene that is more frequently seen
in subject with the disease than in controls.
Candidate genes should have some plausible role in the disease.
3 Types
1. Functional candidate gene - based on potential function of gene
2. Positional candidate gene - based on involvement of a gene to a
marked location after linkage analysis
3. Expressional candidate gene - determined through differences in
gene expression using micro arrays

26. Gene Polymorphism Studies in Periodontitis are focused on the
following candidate genes
1. Cytokines
2. Cell surface receptors
&
Receptors related to antigen recognition
3. Chemokines
4. Enzymes

27. Cytokine gene Polymorphism
 Why is it important?
• Cytokines have pivotal role initiation & progression of periodontal disease.
• Cytokine response differ between individuals.
 I L- 1 gene polymorphism
• The gene 1L - A,1L- B & IL Rn (IL – 1 α IL- β and IL – RA)
located in IL – 1 gene cluster on chromosome 2(2q 13 – 21)
• Multiple polymorphic sites (VNTR, micro satellite and & numerous SNP)
• Kornmen et al(1997) described PAG(Periodontitis Associated Genotype)
• PAG is a composite IL-1 genotype formed of two rare allele at separate SNP
First -889 in IL-1A Promoter region (C-T)
Second +3954 of the IL1 – B gene (C-T)
-889 is later superseded by +4845 G –T

28. Chronic Periodontitis
Positive association (Kornman et al, Galbraith et al ,McDevitt et
al)
No association (Armitage et al ,Cutler et al ,Lang et al)
Aggressive Periodontitis
No association
PAG associate more with Chronic Periodontitis and
does not correlate with aggressive periodontitis.
Functional Studies
Carriage of allele 2 in (-889) locus resulted
in four fold increase of IL - 1α in chronic
Periodontitis.
IL 1 composite genotype patients had
higher level of IL-1 β in GCF
What Does Studies Say?

29. IL - 2 Gene Polymorphism
• IL - 2 in a Pro inflammatory cytokine produced
by TH cells.
• IL - 2 gene is localized in 4q26
• Polymorphism at – 330 and +166 were identified -330
polymorphism (G-T) TT genotype seem to be
2.5 times less likely to develop severe Periodontitis
than GG genotype.

30. IL – 4 Gene Polymorphism
• Il – 4 rescue B limphocytes from
apoptosis and enhance their survival
• IL – 4 gene found in chromosome 5q31.1
• SNP at – 590 position and 70bp VNTR at
intron 2 have been identified.
• No association have been found with
their polymorphism with chronic or
aggressive Periodontitis

31. IL - 6 Gene Polymorphism
• Gene located in chromosome 7p21
• IL – 6 gene polymorphism is associated with
rheumatoid arthritis and bone mineral density
• SNP at – 174(G – C) .
• GG genotype correlated with chronic Periodontitis
susceptibility(but conflicting results in various reports)
• Functional Studies revealed that
Periodontitis patients carrying one or two copies of the
rare allele in the IL – 6 (-174) Polymorphism
had higher serum IL – 6 & CRP concentration.

32. IL - 10 Gene Polymorphism
• Anti inflammatory cytokine
• Gene localized in chromosome 1q31 – 32
• Polymorphism identified are SNP at – 108(G-A), -819(C-T)
and -592(C-A), also micro satellite polymorphism at 5’
flanking region of the gene.
• Conflicting results in different population with respect to
association with chronic Periodontitis.
• Susceptibility for aggressive Periodontitis (ATA/ATA genotype)
• Functional studies revealed that ATA/ATA phenotype
resulted in low levels of IL-10
 IL-13 gene polymorphism
IL-13(-1112(C/T polymorphism) - CC genotype or C allele increases the
risk of AP in non smokers(Chinese population)

33. TNF Polymorphism
• Pro inflammatory cytokine - immuno regulatory function,
stimulate bone resorption.
• TNF gene localized in chromosome 6p21.3(within HLA
complex gene)
• Eight polymorphism in different regions are described
(-1031(T-C), -863(C-A) -857(C-T),-3676(G-A), -308(G-A),
-238(G-A) +489(G-A)
• Polymorphism are associated with rheumatoid arthritis
Sjogren syndrome, SLE, psoriasis and inflammatory bowel
diseases.
• Studies have shown association with Chronic Periodontitis but
not with Aggressive Periodontitis
• Functional studies have shown that -308 allele correlated
with higher TNF Production.

34. TGF β1 Polymorphism
• TGF β1 is described as double edge
sword having both therapeutic and
pathological role.
• Gene localized in chromosome 19q13.1
• Four SNPs are studied.
• SNP at -509(C-T) was associated with
chronic Periodontitis but no association with other
three SNPs.

35. Cell Surface Receptors
Polymorphism studied are on genes
• IL-1/4/6/10 receptors
• TNF receptor (TNFR)
• ILF(interleukin enhancing binding factor)
• ILIRN( interleukin -1 receptor antagonist)
• FCGR(FC gamma receptor)
• ER(estrogen receptor)
• TLR(toll like receptor)
• VDR (Vit D receptor)
• CD14
• IFNGR – interferon gamma receptor

36. FCGR – gene for FcγR Polymorphism
• FCγ R is the receptor for constant region of IgG
• Expressed by leukocyte from both myeloid and lymphoid lineages
• Found in 1q 21 and 1q 23-24
• Three main classes with eight subclasses
Fc γ RIA
Fc γ RI ( CD64) Fc γ RIB
Fcr γ RIC
Fcγ RIIA
Fc γ RII ( CD32) Fc γ RIIB
Fc γ RIIC
Fc γ RIII ( CD16) Fc γRIIIA
Fc γRIIIB

37. Functional bi allelic polymorphism have been identified for FcγRIIA ,FcγRIIIA & IIIB
• FcγRIIA polymorphism – FCγRIIA – R131 – bears arginine at 131 position
or
FCγRIIA - H131 – histidine at 131 position
This difference affects a receptor affinity for IgG2. H131 is more efficient than
R131
• FcγRIII A polymorphism - FC γ RIIIA – 158F(phenyl alanine)
or
FCγRIIIA – 158V (valine)
158 V have more affinity for IgG1 & IgG3 than 158F type
• FCγIIIB polymorphism – NA1 or NA2 caused by four amino acid substitution
Neutorophills with NA2 bind IgG1 or IgG3 less effectively than NA1
Association studies have reveled that FCγIIIB - NA2 was at more risk for AP
and FCγIIIA - 158V ,FCγIIA-H131 at more risk for CP.

38. Hypothetical role of FCγR genotype
in susceptibility to Periodontitis .

39. Cytokine & Chemokine Receptors
• TNF R2(+587) –(T/G) polymorphism is associated with
chronic Periodontitis.
• IL-6 receptor polymorphism is associated with diabetes
and obesity. It may have a role in Periodontitis also.
• IFNGR1(Interfren-γ receptors 1gene
polymorphism(microsatellite) correlated with
Periodontitis
• Not enough studies are there for other cytokine receptors

40. Vit D Receptor Polymorphism
Why is it Important
• Mediators of bone resorption play a role in the
patho physiology of Periodontitis
• Vit D play a role in Ca & P metabolism
• VDR polymorphism are associated with
osteoporosis, osteoarthritis, as well as some
infectious diseases such as TB.
• Vit D and its receptor play a role in phagocytosis
by monocytes and affect monocyte differentiation.

41. Vit D Receptor Gene Polymorphism
Localized in chromosomes 12q12 – 14 .
• It exhibit functional polymorphism associated with
osteocalcin levels and bone mineral density.
• Three polymorphism are studied Taq1
BSM1
Apa1
• Rarer allele associated with Chronic and aggressive
Periodontitis but conflicting results are there in
different population.

42. Gene polymorphism in innate immune receptors.
Why is it important
• Innate immune response is the first line of defense
• Innate immune system recognize PAMP through TLR,
CD - 14 & CARD15
• They connect innate & adaptive responses.
• Gene for CD-14 receptor localized on 5q21-23
• CD14 -260 N allele is associated with severe form of
Periodontitis
• CD14 -159(C-T)polymorphism is also associated
with Periodontitis.

43. TLR Polymorphism
• TLR 2 polymorphism - couldn’t show any association
• TLR 4 Polymorphism - -299 gly(TLR+896) shows
susceptibility to Periodontitis.
-399 Ile is Protective against AP
• TLR 9 polymorphism - 1486C/T
- 1237 C/T
+ 2848 A/G
• TLR 9 haplotype comprising of -1486T, -1237T and
+2848 A may be associated with chronic
Periodontitis (Holla et al 2010)

44. nfMLP(N formyl peptide) receptor gene Polymorphism
• nfMLP ia a structured analog of bacterial
products involved in neutrophyl chemotaxis
• gene localized in chromosome19
• Two SNP at 329(T-C) & 378(C-G) were
associated with aggressive periodontitis.
• They are functional polymorphism resulting
in amino acid changes and which have a
role in receptor binding , G protein
activation and chemotaxis

45. HLA Polymorphism
MHC system is a cluster of genes encoding human
leukocyte antigens which are localized on 6p21.3
A
Class I B Expressed on most nucleated cells
C
MHC
DP
Class II DQ Expressed on antigen presenting
DR cells

46. Why is it Important
It has a major role in regulating immune response
• more than 40 disease , most of which are autoimmune
disease have been associated with the HLA Polymorphism.
• It a highly polymorphic
• more than 150 HLA antigens have been defined serologically
• more than 220 alleles have been identified on one sub class
such as MHC class II DRI

47. • Association Studies have shown that patients with HLA- A9
and B15 genotype is at more risk (1.5-3.5time) for aggressive
Periodontitis.
• HLA-A2 antigens appear to be protective
• HLA – DQB1 associated with early onset Periodontitis(accelerated
T – cell response against Pg)
• HLA-DR4 is having association with periodontal disease
diabetes related complication

48. Enzymes
MMP polymorphism
MMP-1 polymorphism – polymorphism in promoter region
(-1607) is associated with chronic periodontitis.(Conflicting results).
No association with AP.
MMP 2,3,9 are studied but most of the result are –Ve.
Other genes studied are
RAGE(receptor for advanced glycation and products)
ER(estrogen receptor) – associated with CP not with AP.
CCR5(chemokine receptor-5)
MCP1(monotype chemo attractant protein 1)
Lactoferin - an iron binding protein which is bacteriostatic
- Association with AP.
Calprotectin - cytoplasmic protein which is having antifungal,
antibacterial, apoptosis inducing and chemotactic functions.
- No association

49. Is Genetics a risk factor for chronic & aggressive
Periodontitis ?
• Twin Studies and a few association studies pointed to
genetics as a risk modifying factor for chronic Periodontitis.
• Segregation analysis linkage studies and very few
association studies link genetics to aggressive Periodontitis
• Several gene polymorphism have been associated with
both chronic & aggressive Periodontitis
• No single gene of major pathogenic effect have been
identified so far.
• Both chronic & aggressive Periodontitis are not single gene
but polygenic disease and genetic polymorphism may
influence in a complex way acting with genetic variant
and environmental factors

50.  Requirements for providing association
between gene polymorphism & disease
1. The polymorphism must influence the gene product
2. Biases in the study population should be recognized and
controlled
3. Affected gene product should be part of the etiopathalogy of
the disease.
 Issues in genetic association studies ( polymorphism)
1. Ethnic heterogeneity
2. Differences in clinical classification
3. Sample size
4. Choice of controls
5. Complexity of the disease (multi factorial influences)

51.  Why associated polymorphic gene doesn’t cause
Periodontitis always ?
 As gene transcription and influence of structural
variant on this process is context dependent, the influence
of genetic polymorphism will be different in diverse cell
types at different developmental stages and different
environments
 Gene to gene interaction
 Influence of epigenetic factors
 Protein interaction
 Environmental interaction

52. Genetic defects associated with Periodontitis as
a manifestation of systemic disease.
This group include various syndromic diseases
• They are transmitted as Mendelian traits
• They are monogenic diseases
• These diseases clearly demonstrate genetic
mutation at a single locus that determine the
susceptibility to periodontitis.
 They are grouped as
1. syndromes with decreased neutrophil number
2. Syndromes with abnormal neutrophil function
3. Syndromes of metabolic, structural or immune protein
defects

53. Syndromes with decreased neutrophil number
Disease Clinical features Inheritance Gene Gene Function or proposed
disease mediator
Severe
congenital
neutropenia
type 1
Multiple bacterial
infections and
abscesses; death from
sepsis. Acute myeloid
leukemia or
myelodysplastic
syndrome. Oral
ulcerations ,
Periodontitis and oral
candidacies
Autosomal
dominant
Mutations in
the
Neutrophil
elastase
gene ELA2
ELA encodes neutrophil
elastase, a 31-kDa serine
Protease. In vitro,
neutrophil elastase
degrades outer membrane
protein A, a component of
the gram-negative cell
wall
Severe
congenital
neutropenia
type 2
Circulating primitive
myeloid cells; B-cell
and CD4 T-cell
lymphopenia
Autosomal
dominant
Mutations in
the growth
factor –
independent
1 gene GFI1
GFI1 Functions to repress
ELA2.Mutation of GFI 1
results in over expression
of ELA2
GFI1 – role in
hematopoiesis &
neutrophil differentiation

54. Syndromes with decreased neutrophil number(cntd)
Disease Clinical features Inheritance Gene Gene Function
or proposed
disease mediator
Severe
congenital
neutropenia type
3,Kostmann
syndrome.infanti
le
agranulocytosis
Pneumonia, skin
abscess,tonsillitis,lym
phadenitis,bronchitis,p
haryngitis,otitis,oral
ulcers,gingivits,Period
ontitis,aplenomegaly
Autosomal
recessive
Mutations in
hematopoietic cell-
specific LYN
substrate 1
associated protein
X1;HAX1
Lack of the
bactericidal
peptide(CAP-18) -
precursor of LL-37,
inadequate
neutrophil
development.
Severe
congenital
neutropenia
Multiple bacterial
infections and
abscesses ; death from
sepsis
Autosomal
dominant
Mutation on
granulocyte -
colony stimulating
factor gene(G-CSF)
(rare)
Lack of functional
granulocyte –
colony stimulating
factor receptor
Chronic familial
neutropenia
Recurrent oral
ulcerations,Periodontit
is,Premature tooth
loss,finger clubbing,
hypergammaglobinemi
a,neutropenia.
Infections not as
severe as with forms
of severe congenital
neutropenia
Autosomal
dominant and
autosomal recessive
forms
Unkonown

55. Syndromes with decreased neutrophil number(cntd)
Disease Clinical features Inheritance Gene Gene Function or
proposed disease
mediator
Cyclic
neutropenia
Peripheral blood
neutrophil counts vary
from near zero to a most
normal in a 21-day cycle.
Recurring fever and
malaise. Bacterial
infections and aphthous
uclers often accompany
decreased neutrophil
counts. Periodontitis of
varying severity may be
present
Autosomal
dominant
ELA2 ELA encodes
neutrophil elastase, a
31-5Da serine
protease. In vitro,
neutrophil elastase
degrades outer
membrane protein A, a
component of the
gram – negative cell
wall
Inherited
bone
marrow
failure
syndromes
Associated neutropenia
severe Periodontitis
sometimes reported, but
the prevence in most
forms is not known
Autosomal
dominant and
autosomal –
recessive
forms
assorted

56. Syndromes with abnormal Neutrophil function
Disease Other clinical features Inheritance Gene Gene function or
proposed disease
mediator
Chediak-
Higashi
Syndrome
(CHS)
Hypopigmentation of the skin,eyes
and hair. Prolonged bleeding times,
easy bruising, neutropenia,
recurrent infections , abnormal
natural killer cell function ,
periopheral neuropathy, giant
intracellular granules in lysosomes,
periodontitis and oral ulcerations
are associated with severe forms of
Chediak – Higashi syndrome
Autosomal
recessive
Lysosomal
trafficking
regulator
gene LYST
that encodes
the CHSI
protein
The function of the
CHSI protein is
largely
unknown .Defect in
the ability of cells to
to secrete lysosomes .
Deficiency in
cathepsin G
Leukocyte
adhesion
deficiency
type 1
Recurrent bacterial infections,
defective neutrophil mobility,
delayed umbilicial cord separation,
recurrent oral ulcerations,
aggressive periodontits
Autosomal
recessive
Beta-2
integrin
chain;
ITGB2, a cell
membrane
glycoprotein,
Manifest as lack of
integrin β2/αL,
β2/αM, β2/αX,
expression. Lack of
adhesion molecule
CD18 on neutrophils
Leukocyte
adhesion
deficiency
type 2
Mental retardation , short stature,
distinctive facial appearance and
recurrent episodes of bacterial
infections, mainly pneumonia
periodontitis and otitis media
Autosomal
recessive
Mutation of
the SLC35C1
gene that
encodes
glucose
diphosphate-
fucose
transporter.
Impaired neutrophil
mobility, defect in
fucose metabolism .

57. Syndromes of metabolic, structural or immune protein defects
Disease Other clinical features Inheritance Gene Gene function or proposed
disease mediator
Kindler
syndrome
Skin fragility, patchy
hyperpigmentation,
hyperkeratosis of palms and
soles, diffuse skin wrinkling
Autosomal
recessive
Kindlin
1(KIND1)
Kinderline gene express by
many tissues including skin.
Play a role in integrin
signaling of cell adhesion
process.
Cell-cell contact, focal
adhesions, Skin fragility
Papillon-
Lefevere
syndrome
Palmoplantar hyperkeratosis,
severe early-onset Periodontitis
that affects both primary and
permanent dentitions
Autosomal
recessive
CathepsinC
(50
different
mutations)
Inactivation of cathepsin C
results in failures to cleave
and activate the neutrophil
serine proteases cathepsin
G,neutrophil elastase, and
proteinase 3
Haim-Munk
syndrome
(allelic
condition of
Papillon-
Lefevere
syndrome)
Palmoplantar hyperkeratosis,
severe early onset Periodontitis
that affects both primary and
permanent dentitions, acro-
Osteolysis, atrophic changes of
the nails and a radiographic
deformity of the fingers
Autosomal
recessive
Cathepsin C Inactivation of cathepsin C
Aggressive
Prepubertal
Periodontits
Severe early-onset Periodontitis
that affects both primary and
permanent dentitions
Autosomal
recessive
Cathepsin c Inactivation of cathepsin c

58. Syndromes of metabolic, structural or immune protein defects(contd)
Disease Other clinical features Inheritance Gene Gene function or
proposed disease
mediator
Ehlers-Danlos
syndrome
type IV
Only few case reports; not as
clearly associated as ehlers-
Danlos syndrome type VIII
Autosomal
dominant
Type III
collagen
gene(COL3AI)
Decreased levels of
collagen III
Ehlers-Danlos
syndrome
type VIII
It is reported that severe
early-onset Periodontitis
discriinates ehlers-Danlos
syndrome-VIII from other
types of ehlers-danlos
syndrome.patients have skin
hyperxtensibility
fragility,scarring,minimal-to-
moderate joint
hypermobility.
Autosomal
dominant
Linkage at
chromosome
12p13
Unknown,studies of
collagen in these
patients have yielded
conflicting results
Hypophospha
tasia
Premature shedding of
primary teeth,presumably
secondary to defective
cementum hypoplastic
enamel, and aggressive
Periodontitis in some
patients
Autosomal
dominant or
recessive
ALPL Deficient
liver/bone/kidney
alkaline phosphatase
activity

59. Conclusion
 Specific Genetic defects are the causative factor for
syndrome associated Periodontitis (Periodontitis as a
manifestation of systemic disease).
 But no specific genetic risk factor has been identified for
Chronic or Aggressive Periodontitis.
 Genetic factors(around 50genes) influence chronic and
Aggressive Periodontitis in a complex way.
 It is likely that development of Periodontitis in an
individual depends on collective presence of environmental
risk factors and genetic risk factors at a given time point
during the life.
 Genetic information would be valuable in therapeutic
intervention on individualized approach and preventive
strategies of the development of Periodontitis

60. References
 Biology of Periodontal tissues – P.Mark Bartold, A. Sampath
Narayanan
 Clinical Periodontology 10th
edition: Carranza, Neuman &Takei
 Clinical periodontology & Implant dentistry 5th
edition: Jan
Lindhe
 Periodontology 2000 vol 32,2003, 11-25
 Periodontology 2000 vol 35,2004,151-179
 Periodontology 2000 vol 43,2007,102-132
 Periodontology 2000 vol 43,2007,133-159
 Periodontology 2000 vol 45,2007,14-34
 Periodontology 2000 vol 45,2007,95 – 112
 J clin.Periodontology vol 37 2010 , No2, 120-152
 J Periodontal research vol45 2010 , No5, 695-701