This document discusses genetics in relation to periodontitis. It provides background on genetic study designs like segregation analysis, twin studies, and linkage/association studies that are used to identify genes associated with periodontal diseases. Specific genes linked to aggressive periodontitis are mentioned, including mutations in the alkaline phosphatase, cathepsin C, and CD18/CD11 genes. Studies finding autosomal dominant and recessive inheritance of aggressive periodontitis in different populations are summarized. The role of HLA antigens and IL-1 gene polymorphisms in periodontitis susceptibility is also briefly covered.

1. GENETICS IN
PERIODONTOLOGY
Under the guidance of
Prof (Dr.) Rajan Gupta
Presented by
Gaurav didhra

2. CONTENTS
1. INTRODUCTION
2. GENETICAL STUDY DESIGNS
3. AGGRESSIVE PERIODONTITIS IN RELATION TO
GENETICS
4. CHRONIC PERIODONTITIS IN RELATION TO
GENETICS
5. CLINICAL IMPLICATIONS.

3. INTRODUCTION
 Initially the periodontal disease was thought to be environmental in
origin but study done by Loe et al in 1986 in Sri lankan tea
labourers with poor oral hygiene it was found that some developed
periodontitis at a rapid rate whereas other experienced little or no
disease.
 This reason may be explained on the basis of host susceptibility in
terms of genetic variations.
 So the recent focus in periodontology is to identify the genes
associated with the disease susceptibility.

4. BASIC TERMINOLOGIES
 DNA is the basic genetic material for all organisms( except
viruses)
 Within the cell there is nucleolus it contain chromatin and
nucleous chromatin condenses to form chromosomes
each chromosomes have thousand of genes each gene
encodes a particular trait, it may be related to eye colour or
blood group type etc.

5. Que. What is a Gene?
 Gene is a basic molecular unit of heredity located on
chromosomes. It is made up of double stranded structure c/a
DNA with particular nucliotide sequences.
 Several nucleotides combine together with phosphodiester
bond to form a polynucleotide chain.
 Several portions of DNA will help in synthesis of particular
protein that will decide the phenotype of person.

6. BASIC STRUCTURE OF DNA

7.  Mutation in the nucleotide sequence lead to different variant k/a
allele in a population.
 At a given locus an individual is considered homozygous if the allele
are identical and heterozygous if the allele are different.
 Basically alleles are pair of genes that appear at a particular location
on particular chromosomes and control the characteristics such as
blood type and colour.

8.  Genetic marker- Any nucleotide sequence on a particular locus
that is used to map or locate the disease allele
 Mode of inheritance of disease can be monogenic in which only
genes are the causative factor. Or it can be multifactorial where
environmental factors also play important role like in
periodontitis.
 Genes involved in multifactorial diseases are c/a susceptibility
genes/ allele.
 Individuals with these alleles will not develop the disease unless
exposed to deleterious environment like in periodontitis – the
imp environmental risk factors include smoking, poor oral
hygiene, anarobic microorganisms.

9. GENETIC STUDY DESIGN
 1. SEGREGATION ANALYSIS
 They are used to study the inheritance of disease among the families.
 The 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.
 A dominant allele will always determine the phenotype of
individual
 A recessive allele will be inherited only when it is present at
both loci on homologous chromosomes.

10.  Power of segregation analysis was dependant upon the size of
population to study the observed pattern of disease.
 Drawbacks
1. Mode of inheritance among older individual was difficult to
carry out.
2. It was not able to explain the relation b/w environmental and
genetic heterogenecity.

11. 2. Twin Studies
 They are used to study the influence of genetic and environmental
factors on the complex diseases like periodontitis with multifactorial
etiology.
 It covered the drawbacks of segregation analysis
 The subject of interest in twin studies can be monozygote or
dizygotic twins.
 Twin sudies are used to estimate the inheritence of phenotypic
variations among twins that are reared apart or together.
 Any similarities b/w both of them will be attriuted to their shared
genes and dissimilarities will be because of environmental factors.

12. 3. Linkage and Association studies
 They are used to map disease allele to specific regions on
chromosomes
 The probability that the two allele at different loci will
recombine is proportional to the distance b/w them.
 By identifying the genetic markers that are associated with
the disease causing alleles the researchers can alter the
location of disease allele.

13.  Marker and disease allele are used to determine the
inheritance of disease within families
 Generally the inheritance of a disease can be established if
the distance b/w marker and ds. Allele is within 20-30
centimograms (cM).

14.  Linkage disequilibrium is a term that is used when same
marker allele is associated with disease in multiple families.
 To test this association the frequency of allele at a given
locus is compared in subjects with disease and healthy
controls.
 True linkage disequilibrium means when marker and
disease allele lie close to each other on chromosomes and
the chances of disease are more.

15.  The association b/w marker and disease allele may not be
because of genetic origin but it may be under environmental
influence also.
 In 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.

16. AGGRESSIVE PERIODONTITIS IN RELATION TO
GENETICS
 Most of the diagnosis regarding aggressive periodontitis is based
on clinical and radiographic data.
 Because of environmental and genetic heterogenecity very less
studies are carried out regarding genetic mode of inheritance.
 AP is seen to be inherited in many genetic conditions. The
mutant allele may affect the function of phagocytic immune cells,
structure of epithelia, connective tissue and teeth.
 Not all the genes causing AP are studied but up to certain extent
some genes are identified.

17.  Conditions that are genetically identified to be associated with AP
1. Hypophosphatasia- associted with mutation in alkaline
Phosphatase gene ( Ip36. Ip34). Includes cemental hypoplasia,
aggressive periodontitis, premature loss of 1º and 2º teeth. It has
both autosomal dominant and recessive inheritance.
2. Papillon-Lefevre syndrome(PLS)- Autosomal recessive caused
by mutation in cathepsin C gene located at chromosome no. 11.
Cathepsin C is a cystiene protease that play imp. Role in
degrading proteins and activation inflammatroy proenzymes.

18.  However in some patients of PLS the aggressive periodontitis
associated with virulent microorganisms i.e. A.a and periodontal
destruction can be eliminated by removing A.a showing that
aggressive P. is not as a result of genetic mutation but may be as
a result of specific bacterial infection.(Preus HR 1988)
3. Leucocyte adhesion deficiency syndrome – It is of two types type
I and type II. It occurs by mutation in the gene encoding for CD 18
integrin( LAD- I) and CD15 integrin (LAD -II)
4. Chediak Higashi syndrome – autosomal recessive disorder
affecting melanocytes, platelets and phagocytes. In this neutrophills
contain abnormal giant lysosomes that looses their ability to show
phagocytosis.

19. 5. Prepubertal periodontitis- associated with defect in
cathepsin C gene.
6. Ehler-Danlos syndrome - characterised by hyperelasticity of
joints along with defect in collagen causing more periodontal
destruction.

20. SEGREGATION ANALYSIS
 Various studies have been done to show the ineritance of
aggressive periodontitis(AP)among families.
 However there exist variations in the mode of inheritance of AP
because of genetic and environmental heterogenecity.
 Spektor MD in 1985 has shown that both forms of AP i.e.(
prepubertal and juvenile) has genetic mode of inheritance with in the
families.
 Melnick et al in 1976 proposed X linked inheritence of AP because
of females were mostly affected. However the female
preponderance in this study was a bias because they were more
likely to seek dental care and participate in family studies.

21.  Saxen et al in 1980 also showed an autosomal recessive mode of
inheritance of AP among Finnish populations.
 Among the largest US studies coducted till date, an autosomal
dominant mode of inheritance was found among African-american
and caucasian families. (Marazita ML 1994)
 Schenkein in 1994 proposed model of inheritance of localized and
gen. aggressive periodontitis among families. He studied that AP
disease and Ig G2 responsiveness to bacterial LPS are inherited
independantly as dominant trait within families.

22.  Under this model subjects with AP disease and two IgG allele
will develop LAP. And those with one AP allele and one IgG
allele will develop GAP.
 However this study lacked any evidence to explain the effect of
environmental factors like smoking, racial difference on Ig G2
levels.

23. LINKAGE STUDIES
 Only few linkage studies are performed tilll date to explain the
inheritance of AP
 Boughman in 1986 was 1st to report the linkage b/w AP and
specific chromosomal region. By using certain markers they
showed that AP gene was localized on the long arm of
chromosome no. 4 near the gene of Denterogerous imperfecta.
 Recently the AP disease has been linked in 4 families with LAP(
locaized aggressive periodontitis) marker located on
chromosome 1. ( Li Y in 2004)

24. ASSOCIATION STUDIES
 Most of the studies are done on HLA ( Human leucocyte
antigen) because of their role in regulating immune response,
they are shown as genetic risk marker for Aggressive
periodontitis.
 Two antigens that are associated with AP are HLA- A9 and B
15.
 The risk of disease in AP patients with HLA-A9 and B-15
genes is 1.5 – 3.5 times higher then those lacking antigens.
 HLA- A 2 antigens was mostly found in control groups
suggesting their protective role.

25.  Similarly Class II DR 4 antigen associated with type I DM have an
increased risk of developing complications related to periodontitis.
( Rotter JR 1992)
 Similarly HLA-D antigen may mediate the association b/w
periodontitis and DM type I.
 Polymorphism in IL-1 gene is extensively studied because of its
role in progression of periodontitis.
 In humans genes encoding for IL-1 and its receptor antagonists
are cultured on long arm of chromosome no. 2. (Nicklin in 1994)
 Mutation in this coding gene is designated as IL-1ß+. Allele at IL-
1ß+ site is reported to be in linkage diequillibrium with aggressive
periodontitis. (Dayer JK 1997)

26.  The high risk IL-1ß+ allele was more common among African
Americans then Caucasians. Showing that they are at higher risk
of developing aggressive periodontitis.
 Polymorphism was also studied among Vit. D receptor gene, IL-1
receptor antagonist, and mutation of FMLP gene that are
associated with aggressive periodontitis. (Gwin MR in 1999)

27. CHRONIC PERIODONTITIS IN RELATION TO
GENETICS
TWIN STUDIES
 Noak et al in 1940 showed that periodontal conditions of two
identical twins were similar
 Independent twin studies were carried out in Minnesota and
Virginia on Monozygotic twins reared apart and reared
together to show the inheritence of chronic periodontitis (CP)
and it was revealed that in both conditions the similarity in
tooth and arch form and radiographic bone level existed and
is independent of environmental factors.

28.  Mechalowicz et al in 2000 showed that the rate of occurence of
periodontitis was more in monozygotic twins (23%) as compared
to Dizygotic twins ( 8%).
 These studies was independent of environmental factors
showing that gene control only the biologic mode of inheritance
and not the behavioural.
 Twin studies was also done to show whether the host genes
have influence on inhertiance of oral microbiota.
 Chen C et al in 1997 showed that oral microbiota can be
transmitted within families

29.  Mechalowicz and Moore in 1999 showed that host genes may
influence the initial bacterial colonization of O/C but the effect
does not persist in adulthood.
ASSOCIATION STUDIES
Similar to aggressive periodontitis genetic polymorphism also exist
in CP.
Korman et al 1997 showed that individuals with IL-1 genotype are
associated with severe periodontitis in North- korean adults.
Deihl SR in 1999 showed that there is linkage disequilibrium b/w
IL-1α and IL-1ß allele.
They also showed that risk of CP is more among with IL-1ß allele
as compared to those with IL-1α allele.

30.  Korman et al also showed that risk of deveping periodontitis is
more in non smokers with IL-1 genotype.
 Whereas Mc Guire 1999 showed that the tooth loss in smokers
with IL-1 genotype was more as compared to non smokers.
 This showed that interaction b/w IL-1 gnotype and smoking is
poorly understood and more studies are needed to find their
corelation

31. CLINICAL IMPLICATIONS OF GENETTIC
STUDIES
1. Genetic tests regarded as screening tools.
2. They play an imp role in knowledge of specific risk factor
and its genetic association. For example Mc Guire et al in
1999 showed that IL-1 composite genotype individuals are
at increased risk of periodontitis with 2.7 times more tooth
loss and smoking increased risk 8 times more. Showing that
it is an imp. Risk factor and accordingly treatment can be
modified.

32. THANK
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