Genetics of Periodontal diseases

Chronic periodontitis was estimated to have

approximately 50% heritability, and was unaltered after
adjusting for behavioral variables, including smoking

Michalowicz et al. (1991)

Basic genetics
DNA (deoxyribonucleic acid) is the blueprint of life

DNA is packaged into units called chromosomes

DNA nucleotide is made of a molecule of sugar, a

molecule of phosphoric acid, and a molecule called a
Base.
The bases are the "letters" that spell out the genetic code.
DNA contains only four chemical bases or
building blocks: Adenine, Thymine, Cytosine,
and Guanine - called A, T, G, and C, for
short. There are roughly 3.2 billion chemical
bases (A, T, C, G) in the human genome

Each DNA molecule is made up of two long

complementary (related) strands, which are
intertwined like a rope.
This is the "double helix.“
In base pairing, Adenine always pairs with Thymine, and
Guanine always pairs with Cytosine
Since A always pairs with T, and C with G, the
order on one strand dictates the order on the
other. This is called base pairing (bp) and
enables the genome to make copies of itself.
The lengths of double stranded DNA
molecules are frequently given in bp (or
nucleotide pairs).

.
The DNA in each chromosome constitutes many genes
(as well as vast stretches of noncoding DNA, the function
of which is unknown). A gene is any given segment along
the DNA that encodes instructions that allow a cell to
produce a specific product - typically, a protein such as an
enzyme - that initiates one specific action. There are
between 50,000 and 100,000 genes, and every gene is
made up of thousands, even hundreds of thousands, of
chemical bases.
Process whereby DNA encodes for the production of amino acids
and proteins.
1. Transcription 2. Translation
The chromosome constitution of an individual
( karyotype) can be analyzed following tissue
culture of an appropriate sample.
The most commonly used sample is blood (using
Iymphocytes) since it is the most accessible.
Human cells contain two sets of chromosomes, one set
inherited from the mother and one from the father.
(Mature sperm and egg cells carry a single set of
chromosomes.)
Each set has 23 single chromosomes - 22 autosomes and
an X or Y sex chromosome.
(Females inherit an X from each parent, while males get an
X from the mother and a Y from the father.)
Diploid organisms (e.g. humans) have paired
homologous chromosomes in their somatic cells,
and these contain two copies of each gene.
An organism in which the two copies of the gene
are identical — that is, have the same alleles — is
called homozygous for that gene.
An organism which has two different alleles of the
gene is called heterozygous.
Chromosomes vary in shape
depending upon the position of
the centromere, the structure
that holds the two arms of the
chromosomes together,

Based upon size and shape,

chromosomes are divided into
eight groups: A (1 to 3), B (4
and 5), C (6 to 12), D (13 to
15), E (16 to 18), F (19 and 20),
G (21 and 22) and the sex
chromosomes, XX in females
If the centromere is in the middle, the chromosome is
metacentric and the chromosome arms are equal in size.
If the centromere is off center, the chromosome is
submetacentric with a short arm labeled p (for petite) and
a long arm labeled q (the next letter after p).
If the centromere is close to the end, the chromosome is
acrocentric and the very short arm consists of a stalk and
a knob (satellite)
Chromosome banding
become a standard and
indispensible tool for
cytogenetic analysis.,
and several banding
techniques have been
developed::
Q banding: chromosomes
are stained with a
fluorescent dye such as
quinacrine
G banding: produced by
staining with Giemsa after
digesting the chromosomes
with trypsin
C banding: chromosomes
are treated with acid and
The G-banding technique yields a pattern of
alternating light and dark bands reflecting
variations in base composition, time of replication,
chromatin conformation, and the density of genes
and repetitive sequences.
Our genetic material is stored in two
organelles: nucleus and mitochondria

Nuclear genome in which 3.2 miliard

bp are packed in 22 pairs of
autosomes and two sex
chromosomes, X and Y

Human chromosomes are not of equal

sizes; the smallest, chromosome 21, is
54 mln bp long; the largest,
chromosome 1, is almost five times
bigger with 249 mln bp
The description of abnormal karyotypes

First state the total chromosome number,

followed by the sex chromosome
constitution:
46,XX normal female
46,XY normal male

del deletion
dup duplication
ins insertion
i isochromosome
inv inversion
r ring chromosome
t translocation
ter terminal
mat maternal origin
Pat paternal origin
+ additional chromosome
46,XY,del(22)(q21)
A male with 46 chromosomes and a deletion on
chromosome 22, with a breakpoint at band q21
46,XX,t(1 ;6)(p23;q21)
A female with 46 chromosomes and a translocation
between chromosomes 1 and 6 with breakpoints at
band p23 on the short arm of chromosome 1 and at
band q21 on the long arm of chromosome 6
 GENES and Alleles
Genes are
genetic material on a chromosome that code for
a trait. For example, you have a gene for eye
color.
A geneis "a hereditary unit that, in the classical
sense, occupies a specific position within the
genome or chromosome; a unit that has one or
more specific effects upon the phenotype of the
organism; a unit that can mutate to various
allelic forms; a unit that recombines with other
such units".
The DNA in each chromosome constitutes many genes
(as well as vast stretches of noncoding DNA, the function
of which is unknown).
A gene is any given segment along the DNA that encodes
instructions that allow a cell to produce a specific product
- typically, a protein such as an enzyme - that initiates one
specific action.
There are between 50,000 and 100,000 genes, and every
gene is made up of thousands, even hundreds of
thousands, of chemical bases.
A locus is a set of genes that are ordered and are localized in a
same chromosomal location, in a given species.

Recessive genes
Reessive genes can only be expressed in homozygous (aa)
individuals.

There are more heterozygous (Aa) carriers than homozygous (aa)

carriers who actually express the trait.

All three genotypes (AA, aa, Aa) are possible throughout any
population.

Even in carriers that are not phenotypically expressed (Aa), the

recessive allele can be identified in a cross.
The three criteria for identifying recessive genes:
1- The first appearance of the recessive trait within a family
usually is in the children of the unaffected parents.
2- 25% of the children will be express trait.
3- Both males and females can express the trait unless it is
a recessive sex linked gene
Dominant Genes
If a gene (A) is completely dominant, AA and Aa
are phenotypically alike.

Phenotypes specified by single gene

substitutions are called dominants and those that
require homozygous combinations for expression
are called recessives.
Dominants are easier to find than recessives, for
dominants are fully expressed when paired with
either allele.

The individual's genotype may be

homozygous or heterozygous if they express
a dominant trait. In dominant the trait will
be expressed in all generations.
The 4 criteria for identifying dominant genes:
2.If the trait is dominant, it will be expressed in
all generations.
3.The trait is passed from the affected parent to
about 50% of his/her children.
4.Any parent that does not express the trait does
not transmit it to any of his/her children.
5.Both males and females can express and
transmit the trait.
In simple or complete dominance the
heterozygote, even though genetically different,
has the exact same phenotype as one of the
homozygotes.
This leads to the conclusion that Aa is equal to
AA, phenotypically speaking.

The recessive gene is present in the

heterozygote but hidden by the dominant.
Dominance is then considered a physiological
An allele is an alternative form of a gene
Alleles are variations of genes. For example, you
have the allele for brown eye color.
A wild type allele is an allele which is considered
to be "normal" for the organism in question, as
opposed to a mutant allele which is usually a
relatively new modification

Note that some alleles are dominant over others.

That is, if a person inherits both the dominant and
the recessive alleles, the dominant allele will be
the one expressed
There are 4 different types of alleles. Dominant, recessive,
codominant, and incomplete dominant.
Depending on the inheritance of two alleles, a person may
therefore end up having a dominant, recessive,
codominant, or incomplete dominant trait.

In a single-gene trait, only two alleles determine the trait.

In a polygenic trait, more than two alleles control the trait.
A genotype is the actual set of alleles an
organims carries.
For example, you have the genotype Bb since you
have the allele for brown eye color (B) and the allele
for blue eye color (b).
An organism is said to be homozygous for a
certain trait if both it carries two of the same alleles.
It is homozygous dominant if it carries two
dominant alleles and homozygous recessive if it
carries two recessive alleles. The organism in our
example is heterozygous -- it carries two different
alleles.
A phenotype is the expression of a gene. For
example, since you have the genotype Bb with
one dominant and one recessive allele, the
dominant allele (B) will mask the recessive allele
(b) and you will have the phenotype for brown
eyes
Variation occurs whenever the order of the
bases in a DNA sequence changes.

Variations can involve only one base or many bases

Not all variations in the genome's DNA sequences

have an effect. Among the variations that do cause
effects, some are more serious than others. The
outcome depends on two factors: where in the
genome the change occurs, (i.e., in a
noncoding region, coding, or regulatory
region) and the exact nature of the change.
Variation occurs whenever the order of the bases in a DNA
sequence changes. Variations can involve only one base or
many bases
Mutation and Polymorphism
Individual genetic changes that are causal of
disease are typically the result of a genetic
alteration that dramatically alters a protein's
function. Such genetic changes are typically termed
mutations and are rare on a population level,
typically being present in less than 0.1% of the
population.

When a specific allele occurs in at least

1% of the population, it is said to be a
genetic polymorphism.
Common genetic polymorphisms may change the
function of a protein, but usually the change is
relatively minor.

Consequently, the specific protein products of

different alleles may function differently.

These differences in physiological functioning

of different proteins can be enhanced by
certain environmental exposures, e.g. diet,
smoking, or microbial factors.

If the affected protein functions in a biological

process, e.g. inflammatory response to a specific
microbial agent, certain polymorphisms may
Geneticists have traditionally divided genetic
diseases into two broad groups:

1 -Simple' Mendelian diseases

2- Complex' diseases.
Simple 'Mendelian' diseases

Diseases that follow predictable and generally

simple patterns of transmission have been
called 'Mendelian' conditions.
In most cases genetic alterations at a single
gene locus are the major determinant of the
clinical disease phenotype.
These diseases follow a classic Mendelian mode
of inheritance
• Autosomal recessive
• Autosomal dominant
• X-linked recessive
• X-linked dominant
Where there is generally no effect on a person’s
health or development and a single faulty copy of a
gene is present, the mutation is described as
being recessive
Individuals who have a faulty gene copy on one
chromosome, and a working copy of that gene on the
other partner chromosome, are said to be ‘carriers’
of the faulty gene for a particular condition.
Individuals who are ‘carriers’ of a faulty autosomal
recessive gene for a particular condition are genetic
carriers for the condition; they do not carry the
condition in their body, as would be the case if an
For the great majority of conditions that are due
to autosomal recessive faulty genes, genetic
carriers are not usually affected.

Autosomal recessive inheritance refers to

the pattern of inheritance of a condition
directly or indirectly due to a recessive
faulty gene copy located on an autosome
Where both parents are unaffected carriers of the autosomal
recessive faulty gene for a particular genetic condition, there is 1
chance in 4 (25% chance) in every pregnancy that their child will
inherit the faulty gene copy from both parents and be
affected by or predisposed to develop the condition

When only one parent is an unaffected carrier of the autosomal

recessive faulty gene, there is no chance that their child will be
affected by or predisposed to develop the condition
Dominant Inheritance
One parent has a single, faulty dominant gene (D), which
overpowers its normal counterpart (d), affecting that
parent. When the affected parent mates with an unaffected
and non-carrier mate (dd), the offspring are either affected
or not affected, but they are not carriers
In dominant genetic disorders, if one affected
parent has a disease-causing allele that
dominates its normal counterpart, each child in
the family has a 50-percent chance of inheriting
the disease allele and the disorders
In diseases associated
with altered recessive
genes, both parents -
though disease-free
themselves- carry one
normal allele and one
altered allele. Each child
has one chance in four of
inheriting two altered
alleles and developing
the disorder; one chance
in four of inheriting two
normal alleles, and two
chances in four of
inheriting one normal
Examples of Mendelian - type diseases
include
Amelogenesis imperfecta,
Cleidocranio dysplasia,
Papillon–Lefèvre syndrome
When the gene responsible for a Mendelian disease
has been identified, it is often possible to develop a
diagnostic test to identify individuals who carry a
disease-causing mutation in the responsible gene
Genetically complex diseases do not follow a simple
pattern of familial distribution or transmission
These 'complex traits' are ! the result of the interaction of

alleles at multiple different gene loci. Environmental factors

are usually etiologically important, and often necessary, in
the development of complex diseases.
On a population level, complex genetic diseases are much

more common than simple Mendelian diseases, and many

occur with a population prevalence of greater than 1%.

Single nucleotide polymorphisms

SNPs in genes may occur in protein coding

regions (exons) and noncoding regions (introns
and regulatory regions). Many SNPs that occur in
genes have no effect on the encoded protein, but
a large number of SNPs do have an effect on the
gene product.
An SNP is further defined as occurring in at least
1% of the population, and indeed several
disease-related polymorphisms occur at much
higher frequencies (20–50%).
 Methods of genetic analyses

1 - Familial aggregation

Famillial aggregation of a trait or disease can

suggest genetic etiology. However, families also
share many aspects of a common environment,
including diet and nutrition, exposures to pollutants,
and behaviors such as smoking (active and passive).
2- Twin studies

Through the phenomenon of twins, in particular

monozygous twins, who arise from one fertilized egg.
Monozygous twins are genetically identical.
Dizygous twins are only as genetically similar as
brothers and sisters would be, on
average they share 50% of their genes in common
(dizygous twins are from two different eggs and two
different sperm).
 
3 - Segregation analysis
Genes are passed from parents to children in a
predictable manner, and usually segregate in
families as predicted by Mendel’s laws.

Segregation analysis evaluates the relative

support for different transmission models to
determine which model can account for the
observed segregation of a trait through families.
It is most appropriately applied to data sets of
many families to determine the best fitting model.
Segregation analysis does not find or aim to find a
specific gene responsible for a trait.
4- Pedigree Analysis

A pedigree is a diagram of family relationships that uses symbols

to represent people and lines to represent genetic relationships
In a pedigree, squares represent males and circles represent
females. Horizontal lines connecting a male and female represent
mating. Vertical lines extending downward from a couple
represent their children. Subsequent generations are therefore
written underneath the parental generations and the oldest
individuals are found at the top of the pedigree.
In the pedigree above, the grandparents had two children, a son
and a daughter. The son had the trait in question. One of his four
children also had the trait.

The probability that a given gene mutation will produce disease -

4 - Linkage analysis

Linkage analysis is a technique used to localize the

gene for a trait to a specific chromosomal location.
Genetic linkage studies are based on the fact that
alleles at syntenic gene loci in close proximity on
the same chromosome tend to be passed together
from generation to generation (i.e. segregate), as a
unit.

Scientists can follow a specific trait as it segregates

through families of interest and determine whether
the trait appears to segregate with a known genetic
polymorphism that has been localized to a specific
chromosomal location.
5 - Association studies

Genes contributing to common, complex diseases such as periodontitis

have proven more difficult to isolate.
When multiple, perhaps many, genes act with environmental factors to
contribute to disease liability, it is difficult to formulate disease models.
Two types of association analysis are commonly employed in genetic
studies: population-based and family-based.
The population-based approach utilizes a standard case-control design,
in which marker allele frequencies are compared between cases
(affected individuals) and controls (either unaffected individuals or
individuals randomly chosen from the population.
6- International HapMap project

The international HapMap project is being conducted to identify

and catalog the common genetic variants that occur in human
beings.
The project will describe each of the common SNPs in the human
genome., determine the genetic location of each SNP and
characterize how these genetic variants are distributed in several
 Gene tests
 
Scientists looking for a disease gene typically have begun by
studying DNA samples from members of "disease families," in
which numerous relatives, over several generations, have
developed the same illness such as e.g. colon cancer.
Researchers look for genetic markers - easily identifiable
segments of DNA - that are consistently inherited by persons
with the disease but are not found in relatives who are disease-
free. Then, they painstakingly narrow down the target DNA
area, pull out candidate genes, and look for specific mutations.
Once a disease gene has been cloned (copied to get
The DNA probe - lengths of single-stranded DNA
that match parts of the known gene. (This is
possible because, in double-stranded DNA, adenine
in one strand always pairs with thymine in the
other, and guanine pairs with cytosine.)

The single-stranded probe then seeks and binds to

complementary bases in the gene. When the probe
has been tagged with a radioactive atom, the area
of DNA it binds to - the gene - lights up.
 

To find a target gene mutation in a sample

of DNA, scientists use a DNA probe - a
length of single-stranded DNA that matches
part of the gene and is linked to a
radioactive atom. The single-stranded
probe seeks and binds to the gene.
Radioactive signals from the probe are then
made visible on x-ray film, showing where
the probe and gene matched.
Evidence for the role of genetic variants in
periodontitis

1 - Famillial aggregation

A) There are reports in the literature on

familial aggregation of periodontal diseases,
but it is difficult to compare them.
The aggregation within families is consistent with a
genetic predisposition.

However, familial aggregation of periodontal disease

may also reflect exposure to common environmental
factors. Shared environmental factors include
education, socioeconomic grouping, oral hygiene,
shared transmission of bacteria, diseases such as
diabetes and environmental features such as
B) There is evidence for a gene of major effect in
aggressive periodontitis.
Early onset forms of periodontitis appear to be
etiologically complex and heterogeneous
(Boughman et al,1992 , Chung et al 2003).
Although bacterial transmission between subjects
has been suggested to explain aggressive
periodontitis clustering within families, this
observation alone is insufficient to account for
familial clustering.
2 - Twin studies of periodontitis

A) Corey et al. (1993) studied self-reported

periodontal health in 4908 twin pairs and found that
9% of subjects, consisting of 116 identical and 233
nonidenticaltwin pairs, reported a history of
periodontitis.
The concordance rate, or level of similarity in
disease experience, ranged from 0.23 to 0.38 for
monozygous twins, and was much lower (0.08–0.16)
for dizygous twins.
These findings suggest that heritable factors are
B) Michalowicz et al. (1991) studied dizygous
twins and monozygous twins , the mean
probing depth and clinical attachment level
scores were found to vary less for monozygous-
than for dizygous twin pairs, further supporting
the role of genetics in this disease. They also,
investigated alveolar bone height and showed
significant variations related to genotype

Chronic periodontitis was estimated to

have approximately 50% heritability, and
was unaltered after adjusting for
behavioral variables, including smoking
3 - Segregation analysis.
Genetic segregation analysis needs accurate clinical
identification of affected individuals and familial relationships as
well as genetic assumptions of the analysis.

A) Saxon et al 1984
Aggressive forms of periodontitis were hampered by diagnostic
classification issues and by an over representation of affected
females falsely supporting X-linked transmission The
preponderance of the evidence supports autosomal
dominant transmission in North America and autosomal
recessive transmission in certain European populations

B) Marazita et al(1994), studied more than 100 families

segregating aggressive forms of periodontitis; their results
supported an autosomal dominant transmission
They concluded that autosomal dominant inheritance with
approximately 70% penetrance occurred for both Blacks and
non-Blacks. (the probability that a given gene mutation will
produce disease - is referred to as penetrance
The currently held theory on the genetics of
aggressive periodontitis is that
prepubertalperiodontitis, localized aggressive
periodontitis, and generalized aggressive
periodontitis are probably due to a major gene
locus transmitted in an autosomal manner
with reduced penetrance; there is evidence for
both autosomal recessive and autosomal dominant
forms.
The expression ( reduced penetrance) means that some subjects
Aggressive forms of periodontitis are genetically
heterogeneous, meaning that while the mutated
gene responsible for the condition is likely to be
the same in any given family, there are probable
several different genetic loci that, if mutated, can
cause aggressive periodontitis.
Linkage studies in aggressive periodontitis

A) Li and coworkers (2004) reported evidence of a

gene responsible for localized aggressive
periodontitis located on chromosome 1q25.
To date, a gene of major effect for aggressive
periodontitis has not been identified.

 
B) Syndromic forms of periodontitis

Severe periodontitis presents as part of the clinical manifestations of a

number of monogenic syndromes and the gene mutation and
biochemical defect is known for many of these conditions.
A commonality of these conditions is that they are inherited as simple
Mendelian traits due to genetic alterations of a single gene locus.
The significance of these conditions is that they clearly demonstrate
that a genetic mutation at a single locus can impart susceptibility to
periodontitis, and this genetic susceptibility may segregate by different
transmission patterns
3 – Hart et al (2003) identified mutation of the
SOS1 gene in individuals with hereditary gingival
fibromatosis. They shared an irregularity on the
short arm of chromosome 2.
The segment of the chromosome in question was
found to contain 33 genes, any of which could be
causing the gingival overgrowth, and they were
spread out over nearly 5 million bases, or units, of
DNA.
38 family members with HGF shared a single one-
1- Neutrophil functional disorders

A) Defects in the number of surface receptors essential for

cell adhesion of the polymorphonuclearleukocyte, may lead
to increased susceptibility to infectious disease.
Affected homozygotes suffer from acute recurrent infections
that are commonly fatal in infancy. Those surviving will
develop severe periodontitis, which will begin as the primary
dentition erupts.

B) The Chediak–Higashi syndrome is a rare disease

transmitted as an autosomal recessive trait. Those
affected are very susceptible to bacterial infections due to
alterations in the polymorphonuclear leukocyte chemotactic
and bactericidal functions.
2 - Deficiency in neutrophil numbers (neutropenias)

A) Neutrophil deficiency is found in infantile genetic

agranulocytosis, a rare autosomal recessive disease
where polymorphonuclear leukocyte numbers are very low
and which has been associated with aggressive periodontitis.

B) Cohen’s syndrome is another autosomal recessive

syndrome and is characterized by mental retardation,
obesity, dysmorphia(mental disorder that involves a distorted
body image), and neutropenia. Individuals
with Cohen’s syndrome show more frequent and
3- Genetic defects of structural components

A) Papillon–Lefe`vre Syndrome is a condition in

which the cardinal clinical features are severe
periodontitis and great variation in the severity and
extent of palmar plantar hyperkeratosis . Genetic
linkage studies narrowed the Papillon–Lefe`vre
gene locus to chromosome 11 and subsequent
mutational analyses permitted identification of
mutations in the cathepsin C gene in patients with
Papillon–Lefe`vre syndrome (Hart et al 1997).
Mutations of this gene are associated with the loss of
protease activity of the cathepsin C protein.
Additional work has demonstrated that Papillon–
Lefe`vre syndrome and Haim– Munk syndrome (a
slightly different clinical variant within the Papillon–
Lefe`vre syndrome group of disorders) are allelic
variants of cathepsin C gene mutations, as
predicted by( Gorlin et al 2001)
B) Ehlers–Danlos syndrome refers to a collection
of connective tissue disorders characterized by
defective collagen synthesis. Ehlers–Danlos types IV
and VIII are related to an increased susceptibility to
periodontitis and are inherited in an autosomal
dominant manner.
Clinical characteristics of type VIII Ehlers–Danlos
syndrome include fragility of the oral mucosa and
blood vessels, and a severe form of aggressive
Polymorphism studies in periodontitis

In complex diseases, genetic variants at multiple gene loci

contribute to overall disease susceptibility. As such, a
simple cause and effect relationship between a particular
genetic allele and a disease is not possible.
Studies reporting such associations vary in design and
rigor. Association studies ideally should evaluate large
numbers in population-based
studies and have the power to detect a significant
association. The overstating of results has become
commonplace such that rigorous, scientifically principled
approaches are needed to guard against unfounded and
Gene polymorphisms of host response
elements and periodontitis

Data from human and animal studies indicate that

genetic variance can influence the innate,
inflammatory, and immunological response to
microbial infection.
It is
important to realize that most of these studies are
In 1997, Kornman et al. found an association
between polymorphisms in the genes encoding for
interleukin-1a (- 889) and interleukin- 1b (+ 3953)
(termed the composite genotype) and an increased

severity of periodontitis.(if the gene sequences have

been found (+) or not been found (-))

The specific genotype of the polymorphic

interleukin-1 gene cluster (periodontitis
susceptibility trait, PST or composite genotype)
was only associated with severity of periodontitis
in nonsmokers, and distinguished individuals with
Other contradictory reports such as Meiselet al. (2002) stated
that the composite genotype showed a strong interaction with
smoking, an established risk factor
for periodontitis, whereas nonsmokers, even when genotype positive,
were not at any increased risk.
A similarly contradictory study (Papapanou,2001) of 132 periodontitis
patients who were age- and sex-matched ,the composite genotype
and periodontitis with controls, did not show any association between
the composite genotype and periodontitis

Ehmke et al. 1999). Of the 33 patients studied, 16 had the

susceptible composite genotype reported by Kornman et al.
Following 2 years of periodontal maintenance care, no
De Sanctis et al. (2000) demonstrated that genotype
expression did not affect
guided tissue regeneration treatment response at 1 year, but
had a great impact on long-term stability (year 4).
In a 3-year period, patients with a positive interleukin-
1 genotype lost about 50% of the clinical attachment
level gained in the first year and were about 10 times
more likely to experience ‡2 mm clinical attachment
loss when compared to oral hygiene-matched
genotype-negative patients.

The polymorphisms in the interleukin-1 gene cluster linked

Interleukin-1 polymorphism in aggressive periodontitis

Hodge et al. (2001) examined interleukin-1a and interleukin- 1b genetic

polymorphisms in unrelated European white Caucasian patients with
generalized early onset periodontitis and found no significant
differences between patients and controls for any of the composite
genotypes described by Kornman et al.
It was concluded that there was a lack of association between the
interleukin-1 polymorphisms and aggressive periodontitis, which
questions the utility of these candidate genes as markers of
susceptibility.
The studies by Diehl et al. (1999) found that allele 1 rather than
allele 2 of the interleukin-1b + 3953 exhibited polymorphism.

Furthermore, Parkhill et al. (2000) investigated the frequency of

polymorphisms in the genes encoding interleukin-1b in Caucasians
with aggressive periodontitis compared to controls. The frequency
of interleukin-1b genotypes homozygous for allele 1 of the
interleukin- 1b + 3953 SNP was found to be significantly increased
in aggressive periodontitis patients (P < 0.025)
Similar negative findings for this composite
genotype and both chronic and aggressive
periodontitis populations from different racial and
ethnic backgrounds have been demonstrated and
thus the diagnostic utility of the composite
genotype may be restricted to specific populations,
i.e. the results do not appear to be applicable
globally and across ethnic populations, and
Shirodaria et al. (2000) have taken the research further
by attempting an assessment of the functional effect of
the composite genotype in terms of the quantity of
interleukin-1a protein in gingival crevice fluid of severe
chronic periodontitis patients. These researchers found
that allele 2 at position +889 of the interleukin-1a
gene, was associated with a four fold increase in
interleukin-1a as determined by enzyme linked
immunoassay.
Tumor necrosis factor α (TNFα)
The TNF cytokine is crucial to both the immune and inflammatory
responses.
Galbraith et al. (1998) determined TNF genotypes in chronic
periodontitis patients and healthy controls and found no differences in
the three bi-allelic polymorphisms of TNFα (-238, -308, +252).

Craandijk et al. (2002) also found no significant associations

between a different series of four TNFα gene polymorphisms
and periodontitis patients.
One can conclude that, despite major advances in the
awareness of genetic risk factors for periodontal
disease, we are still some way from determining the
genetic basis of both aggressive and chronic
periodontitis

Many studies fail to quantitate, in a meaningful way, the

magnitude of contribution of a particular disease-
associated allele to disease risk.
Periodontitis Diagnostics:

Risk Evaluation with GenoType® PST®

By taking a painless buccal swab, the GenoType® PST®
can be used to determine the individual risk to develop a
profound peridontitis or an implant loss. Patients with a
positive interleukin genotype require an ongoing intensive
therapy and prophylaxis plan in order to prevent loss of
natural teeth or implants.
Genetic Principals of the GenoType® PST®:
Two polymorphisms within the IL-1 gene cluster show a
close association with periodontitis:
1. Interleukin 1A gene, position -889
2. Interleukin 1B gene, position +3953
Within both polymorphisms allele 1 harbors a
cytidin (C), whereas allele 2 carries a thymidin
(T) at the respective position.
In particular, when both genes carry allele 2 a
strong over-production of the local inflammatory
mediator, interleukin-1 will occur.
The GenoType® PST® detects the
corresponding allele combination in patients
allowing an evaluation of the individual
periodontitis risk and future strategies for
therapy
Indications for the GenoType® PST® test:

• patients exhibiting agressive, therapy-resistant

periodontitis for individual therapy planning
• patients with established periodontitis and loss of
attachment for progress assessment
• relatives of PST®-positive patients
for:
• risk assessment before major restorative therapy
• optimization of prophylaxis and recall interval
Interleukin-1 and implant failure

Various recent studies, carried out in the US and

Switzerland, concerning implant failure (Gruica et al. 2002;
Feloutzis et al. 2002) show that smokers, in paticular, who
have tested positive for IL-1 mutations have a higher risk
of experiencing implant loss.
Up to 50% of PST®-positive smokers had implant
complications, with attachment loss in recall being 3 times
higher.
It is highly recommended that smokers who have
experienced tooth loss as a result of periodontitis
should be tested for the IL-1 genotype, not least for
the security of the implant practioner. GenoType®
PST®-positive patients, who are smokers and who do
not stop smoking or decline a regular recall (f. ex.
four times a year plus prophylaxis), might only be
granted a limited guarantee for implant therapy.
Smokers who test negative for genetic IL-1 mutations
should, at the least, attend an intensive recall, while
non-smokers who are genetically negative only