genes

1. Rutu dabhi
MDS 3nd yr
Deptof Periodontology
Guided by:
Dr Surabhi Joshi
Dr Santosh Kumar
Genetics and
periodontal disease

2. INTRODUCTION
⚫Bacteria cause periodontal disease, but other
factors determine how severe that disease will
become and how specific a patient responds to the
therapy.
⚫Recently, the clinical severity of periodontal
disease was evaluated in 117 sets of adult identical
(monozygous) and fraternal (dizygous twins. It
was determined that around 48-59% of the clinical
severity of the disease was explained by genetic
factors.

3. LEADING PERIODONTAL DISEASE
CONCEPT
Three popular assumptions guided periodontal
treatment:
⚫Populations with poorplaque control and limited
professional care have widespread severe
periodontitis.
⚫Individualswith poorplaque control for many
years havesevere generalized periodontitis.
⚫The severity of disease depends on the
combination of the bacterial challenge (ie plaque
control) and length of timeof exposure to bacterial
challenge.

4. CURRENT CONCEPTS
⚫Periodontitis requires specific bacteria for initiation
and progression of attachment lossand bone loss.
⚫There is a ‘normal’ host response to this bacterial
challenge.
⚫Although the normal tissueresponse is primarily
‘protective’, italsocauses tissuedestruction.
⚫Healing and repairareconstantlygoing on in the
periodontal tissues.
⚫In majority individuals with moderate bacterial
challenge, protectionand repairdominatedestruction.

5. ⚫Some patients have ‘altered’ host responses and
develop more severedestruction.
⚫Altered host responses may develop from a) heavy
bacterial challenge and b) presence of disease
modifiers that reduce the protectivecomponentof
the host responseoramplify thedestructive
component.
⚫Examples of disease modifiers include: smoking,
diabetes and IL-1 geneticvariations.

6. DISEASE MODIFIERS
⚫The factors thatdetermine severityand response to
treatmentareoften called disease modifiers.
⚫These, when present in patient, change the trajectory
of clinical diseaseexpression overtime.

8. INTRODUCTION TO GENES
⚫The human genome is made of DNA.
⚫Just before each cell undergoes division, it
condenses to form chromosomes.
⚫The DNA is a twisted ladder, a double helix in
which the rungs of ladder are pair of compounds
called nucleotide bases.
⚫Each nucleotide base is attached to two supporting
backbones.
⚫A=T and G=C

10. ⚫There are estimated to be 25,000–50,000 different
kindsof genes in the human genome.
⚫Genes can exist in different formsorstates.
⚫Geneticists refer to the different forms of a gene as
allelic variants or alleles. Allelic variants of a gene differ
in their nucleotide sequences.
⚫When a specific allele occurs in at least 1% of the
population, it is said to be a genetic polymorphism

11. ⚫Polymorphismarises as a resultof mutation.
⚫The different types of polymorphisms are typically
referred to by the typeof mutation thatcreated them.
⚫Single nucleotide polymorphism (SNP):
The simplest type of polymorphism results from a
single base mutation which substitutes one nucleotide
for another.
The frequency of SNPs across the human genome is
estimated atevery 0.3–1 kb

12. ⚫Restriction Fragment length polymorphism (RFLP)
Digestion of a piece of DNA containing the relevant site
with an appropriate restriction enzyme could then
distinguish alleles or variants based on the resulting
fragmentsizesviaelectrophoresis.
⚫Insertion-deletion polymorphism
Results from insertion ordeletion of a section of DNA.
Most common type is the existence of variable numbers of
repeated baseor nucleotide patterns in agenetic region

13. ⚫Kinane and Hart (2003) presented the classic
relationship among phenotype, environment, and
genotype as follows:
Phenotype = Environmental risk factors (smoking
status, plaque control, socio-economic status,
diabetes, etc.)
+ genotype (includesgene–gene interactions)
+ genotype * environment (that is the interaction
between environmentand genotype).

14. ⚫ It has been widely accepted that the differences among individuals at
risk fordeveloping mostdiseases havea substantial inherited pattern.
ENVIRONMENTAL
FACTORS (diet,
smoking,
preventivecare,
exposure to
pathogens)
GENETIC
FACTORS
INTERACT WITH EACH OTHER TO DETERMINE
PERSON”S HEALTH OUTCOMES.
Determines if and when the disease affects the person, how fast and how
severely symptoms of the disease progress and how the person responds to
different treatments in terms of both side effects and success of alternative
therapies.

15. DISEASES where GENETIC componentof the risk PREDOMINATES
and ENVIRONMENTALdifferences playa MINOR ROLE:
CYSTIC FIBROSIS
MUSCULAR DYSTROPHY
DISEASES where ENVIRONMENTAL componentof therisk
PREDOMINATES and GENETIC COMPONENT playa MINOR ROLE:
INFECTIOUS DISEASESeg. HIV
CANCERS like mesothelioma (associated withasbestosexposure)

16. ⚫Most cases of periodontitis appear to fit this complex
genes and environmental model.
⚫The inherited variation in DNA has a role roughly equal
to that of the environment in determining who remains
periodontally healthyversus who is affected by thisdisease.
⚫In genetic studies, over 23,000 genes need to be
considered as potential hypothesis or candidates for
being disease risk factors.

17. GENETIC AND GENOMIC METHODS OF THE 21ST CENTURY
Human Genome Project officially began in 1990.
⚫ Genomicadvances have contributed very little toadvanceour
understanding of the molecular-pathologic causes of
periodontitisorways for improving treatment through
‘individualized approach’, based on patient’s inherited
genetic variation.
⚫ Recently, progress has been realized based on newlyavailable
genomictools and approaches of
Genome Wide Association Studies (GWAS, pronounced
“geewas”)
“next generation” DNA sequencing.

18. PATTERNS IN POPULATION AND PEDIGREE
⚫ Genetic epidemiology: that field of research that unearth the
complex interactions between genes and environment that
underlie individual differences in diseasesusceptibility.
⚫ Populationsadapted genetically to their local environment.
NATURAL SELECTION (Differential survival or
reproduction)
Eg. Sickle cell hemoglobin variant that protects against the
infectiousdisease malaria. It is common in areaswhere malaria-
borne parasite is an endemic because it provides strong
protection against this disease.

19. ⚫Anotherexampleof natural selection:
Abilitytodigest the milk sugar lactose as an adult that
evolved in Europeans in conjunction with the
domestication of dairycattle over 8000 yearsago.
⚫Genetic Drift
Also causes populations with little or no migration
between them to differentiate genetically over the
time, so one cannot assume that every population
differenceobserved has a functional biological basis.

20. ⚫Comparison of periodontitis in different populations
across the globe is extremely challenging because of
the lack of calibrated examiners and standardized
disease definitions.
of disease occurrence or severity in
(monozygotic) versus nonidentical
⚫Comparison
identical
(dizygotic) twins is a very powerful
distinguishing between effects
method for
caused by
variation in genes versus factors in environment.

21. If VARIATION among individuals in diseasesusceptibilityorseverity is
caused ENTIRELY BY FACTORS IN ENVIRONMENT : pairs of
identical twins are no more similar to each other than pairs of
nonidentical twins.
If VARIATION among individuals in disease susceptibility or severity is
caused ENTIRELY BY GENETIC FACTORS : genetically identical twin
pairs will be more similar to each other than nonidentical twin
pairs.
This is because identical twins share 100% of the same genes, whereas
non identical twin pairs share only 50% of their parent’s genes on
average.

23. FAMILY STUDIES
⚫The aggregation of diseases within families strongly
suggestsa genetic predisposition.
important to consider the shared
and behavioral risk factors in any
⚫Thus, it is
environmental
family.
grouping, oral
⚫These would include
hygiene,
education, socio-economic
possible transmission of
bacteria, diseases such as diabetes, and environmental
features such as passivesmoking, sanitation, etc.

24. ⚫Some of these factors, such as lifestyle and
behavior and education, may be under genetic
control and may influence the standard of oral
hygiene.
⚫The complex interactions between genes and the
environment must also be considered in the
evaluation of familial risk for the periodontal
diseases (Kinaneand Hart 2003).

25. TWIN STUDIES
• .
⚫MONOZYGOUS TWINS ARISE FROM A SINGLE
FERTILIZED OVUM AND ARE THEREFORE
GENETICALLY IDENTICAL AND ALWAYS THE
SAME SEX.
⚫DIZYGOUS TWINS ARISE FROM THE
FERTILIZATION OF TWO SEPARATE OVA AND
SHARE, ON AVERAGE, ONE HALF OF THEIR
DESCENDENT GENES IN THE SAME WAY AS
SIBLINGS DO.
characteristics of twins is a
⚫Studying phenotypic
method of differentiating

26. ⚫Any discordance in disease between monozygous twins
must be due toenvironmental factors.
⚫Any discordance between dizygous twins could arise
from environmental and/orgeneticvariance.
⚫Therefore, the difference in discordance between
monozygous and dizygous twins is a measure of the
effects of the excess shared genes in monozygous
twins, when the environmental influence is constant
(Hodge and Michalowicz 2001).

27. POPULATION STUDIES
⚫A genetic polymorphism is the long-term occurrence
in a population of two or more genotypes that could
not be maintained byrecurrent mutation.
⚫ A significant difference in the frequency of a specific
polymorphism, between a diseased group and a
control group, is an evidence that the candidate gene
plays some role in determining susceptibility to the
disease.
⚫An association indicates that either the candidate gene
directly affects disease susceptibility or that it is in
linkage disequilibrium with (very close to) the disease
locus.

28. ⚫This method can help to elucidate the pathogenesis of
a disease process, identify causal heterogeneity, and
ultimately identify individuals most at risk for the
disease.
⚫ In population studies, it is important to clearly define
thediseasestatus.
⚫ Likewise, because of the possibility of racial
heterogeneity, it is important to insure that the patient
and control groups are racially matched (Hodge
andMichalowicz 2001).

29. HERITABILITY
⚫It estimates the portion of all variations in the trait
that is attributable to inherited genetic variations.
⚫Traits whose variation is determined entirely by
differences in environmental exposure have
heritability of 0.0.
⚫Traits with variation attributable solely to genetic
differences have heritability of 1.0
⚫Heritabilitiesare sometimes reported as a percentage
ranging from 0 to 100%.
⚫Most human diseases and non disease traits fall in the
middle of this range between 0.25 and 0.75.

30. ⚫Eg. Type II diabetes havea heritabililtyof 0.26 and
abnormal glucose intolerance has 0.61 in one study.
⚫For periodontal disease, only chronic periodontitis
occur frequentlyenough to have been studied using
the twin design.
⚫Twotwin studies of modest size (110 and 117 pairs )
have been reported, and these estimate heritability
of measuresof chronic periodontitis ranging between
40% and 80%, thus clearly implicating genetic
variation in disease risk.

31. HERITABILITY OF GINGIVITIS
⚫It is feasible that genes implicated in the regulation of
inflammatory process of periodontal tissues associated
with plaque accumulation may play a role in
explaining the individual variability in the severity of
both plaque-induced gingivitis and destructive
periodontitis (Dashash etal. 2007).
⚫Periodontal disease development and progression can
be caused by MMPs produced by both infiltrating and
residentcellsof the periodontium.

32. ⚫One of the most important MMPs, MMP-9 (also
known as gelatinase B or 92-kD type IV collagenase), is
activeagainstcollagensand proteoglycans.
⚫The coding gene is located on chromosome 20q11.2-
q13.1, and several polymorphisms have been detected
in the MMP-9 gene (Vokurkaetal. 2009).

33. GENES ASSOCIATED WITH GINGIVITIS RISK:
⚫ IL-1 cluster, IL-6,10, 12,18
⚫ MMP-9
⚫ TNF
⚫ Fibrinogen
⚫ LT-A.

34. HERITABILITY OF AGGRESSIVE PERIODONTITIS
⚫Some types of aggressive periodontitis seem to be
inherited in a Mendelian manner, and both autosomal
modesand X-linked transmission have been proposed.
⚫Most of the evidence for a genetic predisposition to
aggressive periodontitis comes from segregation
analyses of families with affected individuals in two or
moregenerations
⚫The results in different sets of families are consistent
with both autosomal-dominant and autosomal-
recessive inheritance, as well as X-linked dominant
inheritance, but no single inheritance mode that
would include all families has been established (Meng

35. GENES ASSOCIATED WITH AP RISK:
⚫IL-1 cluster, IL-4,6,10,12,13,18
⚫TNF-a
⚫TGF-b
⚫Vit D receptor
⚫ Estrogrn receptor
⚫LF
⚫RANK/RANKL/OPG,
⚫ MMP 1,2,3,9,
⚫TIMP
⚫CD14
⚫ Cathepsin C, IFN-gamma.

36. Polymorphisms in genesof
⚫Cell-surfacereceptors for immunoglobulins (Fc)
⚫Formyl-methionyl-leucyl-phenylalanine (FMLP)
⚫Human leukocyticantigen (HLA)
⚫Vitamin D
Are promising candidates forsusceptibility
assessmentof aggressive peridontitis.
(Yoshieetal. 2019).

37. HERITABILITY OF CHRONIC PERIODONTITIS
⚫In contrast to aggressive periodontitis, chronic
periodontitis does not typically follow a simple pattern
of familial transmissionordistribution.
⚫The twin study is probably the most popular method
that supports the genetic aspects of chronic
periodontitis.
⚫This study substantiates the contribution that genes
makevs. theenvironment in a phenotypicexpression.

38. ⚫Michalowicz et al. (1991) examined the relative
contribution of environmental and host genetic factors
to clinical measures of periodontal disease through the
study of twins reared together and monozygous twins
reared apart.
⚫Heritability estimates indicated that between 38 and
82% of the population variance for these periodontal
measures of disease may be attributed to genetic
factors.

39. ⚫Corey et al. (1993) revealed that approximately half of
the variance in disease in the population is attributed
togeneticvariance.

40. CANDIDATE GENES FOR CHRONIC
PERIODONTITIS
⚫Interleukin-1, 2, 4, 6, 10
⚫ Fcg receptor
⚫ TNF
⚫Vitamin D receptor

41. STUDY DESIGNS FOR IDENTIFYING THE DNA
VARIANTS
⚫LINKAGE ANALYSIS
 A technique used to mapa gene responsible fora trait to a
specific location on achromosome.
 These studies are based on the fact that genes that are
located close toeach otheron thechromosomes tend to be
inherited togetheras a unit.
 Thesegenes aresaid to be linked.

42. ⚫It requires use of initially very expensive DNA
markers , thiswasoriginally onlyconsidered justified
after finding strong evidence of a genetic basis for a
trait using segregation analysis or family aggregation
analysis.
⚫Drawback: Manydiseasesarecaused by multiple
genes (each contribute to a small amount to the
phenotype/disease/ trait).
⚫It has extremely low statistical power for complex
diseases and in which there is extensive
heterogeneity among different families that have
different combinations of susceptibility genes
and environmental exposures.

43. ASSOCIATION ANALYSIS
⚫Thisanalysis aims to identify which genes areassociated
with thedisease.
⚫It includes CANDIDATE GENE APPROACH, a gene
mapping approach that tests whetherone allel of agene
occurs more often in patients with the disease than in
subjects without thedisease.
⚫Candidate genes are chosen on the basis of their known
or presumed function (i.e. they have some plausible role
in the disease process such as producing a protein that is
important in disease pathogenesis).

44. ⚫Theseare sometimes referred toas case control studies .
⚫Genotype frequencies of an inherited DNA variant for a
group of periodontitis cases are statistically compared
to periodontally healthy control subjects.
⚫If the genotype frequencies differ so greatly that the
resultsarevery unlikely tooccur bychance, it is concluded
that thegenotype that is morecommon in cases than
controls isassociated with increased disease risk.

45. ⚫ADVANTAGES:
It is a boon for discovery of inherited genetic
variation important for a wide range of complex
diseases including diabetes, cardiovascular
disease, metabolic disorders, obesity, and mental
illness.

46. SEGREGATION ANALYSIS
⚫Statistical analysis of the patterns of transmission of a
disease in families in an attempt to determine the relative
likelihood that the disease is caused by a single gene
with dominant or recessive inheritance, by multiple
genes or entirely by variation in exposure to risk
factors.
⚫This is relatively straightforward for traits in which
mutation in a single gene causes the disease to
develop with nearly 100% certainty in carriers, whereas
persons who donot inherit the mutation are at little or
no risk.

47. ⚫Eg. Huntington’s disease is a sinle dominant gene disorder
because it is transmitted with 50% probability to offspring
of affected individuals
⚫Parents of cystic fibrosis individuals are affected rarely and
25% siblings areaffected .

48. HIGHLY COMPLEX
DISEASES
High risk gene
does not
automatically
lead to
development of
the disease
(REDUCED
PENETRANCE)
Several genes or
even dozens od
different genes
may influence
disease
susceptibility
(OLIGOGENIC
INHERITANCE
and GENETIC
HETEROGENEITY
)
Combination of multiple genetic and environmental factors
make thechallengeof deciphering genetic mechanisms by merely
observing transmission patterns in families using the
segregation analysis.
Environment
al exposures
arealso
important
modifiers of
diseaserisk.

49. GENETIC MARKER
⚫It can be any type of biomolecule or assay that
allows us to read inherited differences among
individuals in their DNA sequences.
⚫Blood groups, protein isozymes, and human
leukocyte antigen (HLA) were the first developed
markers.
⚫Recentlydeveloped : “next generation” DNA
sequencing methods.

50. GENOME WIDE ASSOCIATION STUDIES(GWAS)
⚫Theentire human genome is searched.
⚫Here, about half of the statistically definitive findings
point togenes thatexperts in the field had no
suspicion whatsoever were involved in the disease’s
etiology.
⚫This allows the researchers to open up entirely new
pathways for investigation that may lead to insights
about thedisease’s biologic mechanism and suggest
novel molecular strategies for pharmaceutical or other
therapeutic interventions.

51. PERIODONTITIS IN GENETIC SYNDROMES AND
OTHER DISEASES
⚫Diseases that follow predictable and generally simple
patterns of transmission have been called Mendelian
conditions.
⚫These diseases follow a classic Mendelian mode of
inheritance (autosomal dominant, autosomal recessive, or
X-linked).
⚫Usually, the prevalence of these Mendelian conditions is
rare (typically much less than 0.1%), with theexception of
some unique populations that have been isolated from
other human populations.

52. PAPILLON-LEFEVRE SYNDROME
differentiation
⚫Rare autosomal recessive congenital
disorderof chromosome 11p14-q21.
⚫Occurs in children from consanguineous marriages.
⚫Gene responsible: Cathepsin C, lysosomal protease
(Toomesetal).
⚫Cathepsin C is suggested to be implicated in a wide
variety of immune and inflammatory processes
(Toomesetal).
⚫Prevalence : 1-4 per million, equal in males and
females. (Hattabetal. 1995)

53. ⚫Twoessential featuresof Papillon-Lefèvresyndrome:
⚫ Hyperkeratosis of the palms and soles (either diffuse
or localized) and generalized rapid destruction of the
periodontal attachment apparatus resulting in
premature loss of both primary and permanent teeth
(Deas etal. 2003).

54. ⚫External signs are hyperkeratosis of the palms and
soles (Kressin etal. 1995).
⚫Changes in the skin observed by electron microscopy
revealed the diminution of the tonofibrils, alterations
of the keratohyaline granules, and acanthosis in the
stratumspinosum (Kressinetal. 1995).

55. ⚫INTRAORALLY, periodontal symptoms affect
primary and permanentdentitions.
⚫Extensive loss of periodontal attachment
accompanied by generalized, severe, and rapid
destruction of the alveolar bone, that frequently
lead to premature tooth loss.

56. the gingiva demonstrates
collagen
epithelial
synthesis,
⚫Histologically,
hyperplasia,
parakeratosis,
increased
acanthosis, and focal aggregates of
lymphocytesand plasmacells.
⚫In addition, reduced osteoblastic activity and reduced
thickness of cementum have been described (Ghaffer
etal. 1999; Hattabetal. 1995).

58. ⚫Virulent gram-negative anaerobic microbiota has been
considered to be an important initiator of the
destructiveperiodontitisobserved in these patients.
⚫Aggregatibacter actinomycetemcomitans has been
reported to be the majorperiodontal pathogen.
⚫ Capnocytophaga gingivalis, Eikenella corrodens, black-
pigmented Bacteroides, and Fusobacterium spp :
subgingival periodontal lesions in Papillon-Lefèvre
syndrome patient (Ishikawa et al. 1994; Lundgren et al.
1998; Rudigerand Berglundh 1999; Velazcoetal. 1999).

59. Papillon-Lefèvresyndrome has been associated with
⚫decreased neutrophil chemotaxis
⚫reduced random neutrophil migration
⚫impaired neutrophil phagocytosis
⚫reduced myeloperoxidase activity
⚫increased superoxide radial neutrophil production,
associated with a decreased lymphocyte response to
pathogens (Lundgren etal. 1998; Velazcoetal. 1999).

60. EHLER DANLOS SYNDROME
⚫Also known as dystrophia mesodermalis and
fibrodysplasia elasticageneralisatica.
⚫Heterogenous group of inherited disorders of
connective
ligaments,
tissue,
joints,
which
eyes,
may affect the skin,
and vascular system
(Reichertetal. 1999).
⚫EDS is divided into 11 types in accordance with
clinical, genetic, and biochemical features
(Majorana and Facchetti 1992).
⚫

61. The primary cause may be a
⚫Type I or type II collagen deficiency, a lysyl
hydroxylase deficiency
⚫Deletion of N-telopeptide, or
⚫Disorders of copper homeostasis and
fibronectin defects (Reichertetal. 1999).

62. ⚫Immunological analysis revealed that the
concentrations of IgA in saliva and IgA, IgG, and
IgM in serum were within normal limits, with
unpaired phagocytic capacity of the peripheral
blood leukocytes (Reichertetal. 1999).
⚫The temporomandibular joint often demonstrates
profound laxity in conjunction with generalized
joint mobility and dislocation (Fridrich etal. 1990).

63. ⚫Periodontal conditions have been reported with EDS
types I, VII, and VIII.
⚫ Defective dentinogenesis, resulting in aplasia or
hypoplasia of root development affecting the
mandibular incisors, and predisposition for localized
periodontal diseasewas reported in EDS type I.
⚫Radiographic appearance of a bulbous
enlargement of the roots together with pulp
stones at other teeth were reported.

64. ⚫EDS type VII is an autosomal dominant/ recessive
disease.
⚫Poor healing afterextractions
⚫Prevelanceof dental caries
⚫A radiographic evidence of pulp stones, and/ or
malformed teeth have been described.

66. EDS type VIII is an autosomal dominant form
characterized by
⚫Fragile skin
⚫ Abnormal scarring
⚫Early onsetof periodontal disease, with premature
loss of the permanent teeth.
⚫Fragility of thealveolar mucosa and increased
bleeding tendencies have also been suggested

67. EDS can also beassociated with
⚫Ligneous periodontitis (generalized
membranous gingival enlargement due to an
accumulation of fibrin deposits associated with
severealveolar bone loss)
⚫Plasminogen deficiency seems to play a
central role in its pathogenesis.

68. CYCLIC NEUTROPENIA
⚫Rare condition, characterized by cyclical depletion
of polymorphonuclear leukocyte numbers,
typically in 3-week cycles, although this can be
between 2 and 5 weeks.
⚫Episode of neutropenia is usually short, but the
patient polymorphonuclear leukocyte count never
returns to normal
blood-cell count
levels, and the differential
for polymorphonuclear
leukocytes is at least 40% less than normal levels.

69. Periodontal manifestations include
⚫Inflamed gingiva
⚫Gingival ulceration
⚫Periodontal attachment, and bone loss (Kinane
1999; Rezaei et al. 2004).

70. CHEDIAK HIGACHI SYNDROME
⚫It is a rare autosomal recessive disease
function of
associated with impaired
cytoplasmic microtubules or microtubule
assembly in PMNs (Oh et al. 2002).
⚫The susceptibility to infections, although
humoral and cellular immunity are normal,
leads to early death (often before 5 years of
age).

71. ⚫Thedisease reveals itself periodontally by Severe
gingivitisand
⚫Rapid lossof attachment, leading toexfoliation of the
teeth.

72. ⚫CDGs (formerly carbohydrate-deficient
glycoprotein syndrome) are a heterogenous
group of autosomal recessive disorders
defects in the N-
characterized by
glycosylation pathway and subsequent
aberrant formation of glycoproteins.
⚫CDG-IIc is caused by mutations in the GDP-
fucose (Fuc) transporter (encoded by
FUCT1).

73. nonfucosylated oligosaccharides
⚫This syndrome is characterized by
and
presents with severe mental retardation
and immunodeficiency due to an adhesion
defect of the leukocytes (probably due to
absence of a-1,3-fucosylated sialyl-Lewis
selectin ligands).
⚫Diagnosis is based on oligosaccharide and
mutational analyses.

74. COMMON GUIDELINES FOR
ASSOCIATION STUDIES
⚫Candidate genesarechosen on the basis of known or
presumed function that are thought to have some
plausible role in the disease.
⚫Three typesof CANDIDATE GENES:
⚫Functional
⚫Positional
⚫Expressional

75. ⚫Functional genes: derived from an existing knowledge of
the phenotype and the potential function of gene
involved after clinical or physiological studies of affected
individuals.
⚫Positional Genes: based on the involvement of genes to a
marked locationaftergenetic linkageanalysis.
⚫Expressional Genes: determined through differences in
geneexpression using microarrays.
Some issues and concerns should be addressed (Yoshie et
al. 2007) to produce scientifically sound and meaningful
disease-association studies

76. CLINICAL UTILITY OF GENETIC
KNOWLEDGE
⚫Thediscoveryof the association between polymorphisms
in IL-1 genes and severity of periodontitis has been
described as a major breakthrough in clinical practice,
and theobserved increase in risk due to this singlegenetic
factor has been confirmed in a population of “typical” dental
practice patients.
⚫The clinical test forsuch a genetic risk has been proposed
as a component of the risk assessment profile for
chronic periodontitis that can be used to provide a
rationale forexplaining individual patient susceptibility,
providing early preventive or therapeutic intervention,
and allowing superior prognostic capabilities
(Schenkein 2002).

77. CONCLUSION
⚫Genetics are a major determinant of the severity of
chronic periodontitis in adults.
⚫It must be emphasised that this type of genetic
influence is different from the “single gene” defects
(Tay Sachs) or chromosome abnormalities (Down’s
syndrome) in which a genetic factor causes a
disease.
⚫It is likely that a few genetic variations with a high
prevelance in the population will be found to
influencechronic periodontitis.

78. THANK YOU
!!!