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1. GENETIC POLYMORPHISM AND
PERIODONTAL DISEASE
By Eman Farouk

2. CHROMOSOME
A nuclear structure that contains genetic information.
Humans have 46 chromosomes that are arranged in 23
pairs. There are 22 pairs of autosomes and one pair of
sex chromosomes (either XX or XY).

4. GENE
the basic physical and functional unit of heredity. Gene is
segment of DNA on a chromosome. Some genes act as
instructions to make proteins.

5. GENOME
• The entire hereditary information of an organism. This
term refers to all of the genes and other nongene
portions of DNA carried by an individual cell.

6. • Genotype The genetic makeup of an organism or cell as
distinct from its expressed features or phenotype
• Phenotype The observable characteristics displayed by an
organism (e.g., morphology, development, gender, eye
color, physiologic properties, behavior). Phenotype results
from the expression of the organism’s genes as well as
from the influence of environmental factors and
interactions between the two

7. LOCUS
• The physical
location that a gene
occupies within a
chromosome.

8. MUTATION :
• It is a very rare
change in a
nucleotide which
doesn’t present in
many individuals

9. POLYMORPHISM
• It is kind of mutation but considered to be a normal
variant when a specific allele exceeds more than >1% of
population

12. mutations in a single
gene are both necessary
and sufficient to produce
the clinical phenotype
and to cause the disease
Genetic diseases
Simple mendelian diseases
(monogenic disorders)
Complex genetic diseases
(polygenic disorders)
In complex disorders with multiple causes,
variations in a number of genes encoding
different proteins result in a genetic
predisposition to a clinical phenotype.
Environment and life-style are major
contributors to the pathogenesis of
complex diseases.
The genetic alterations that contribute
to complex diseases are called
polymorphism.

13. • E.g. syndromic periodontitis
(syndromes, which have
periodontal disease
manifestations as part of
syndromic manifestations are
Papillon Lefevre syndrome,
Chediak- Higashi syndrome, Ehler-
Danlos syndrome, cyclic
neutropenia, and leukocyte
adhesion deficiency
Genetic diseases
Simple mendelian diseases
(monogenic disorders)
Complex genetic diseases
(polygenic disorders)
E.g. Non syndromic periodontitis

15. • Periodontitis is a multi-factorial disease. Genetics is
considered a susceptibility factor in relation to
periodontitis. Among the various study designs,
population studies are used to find the frequencies of
polymorphisms of candidate genes, by comparing
between cases and controls.

17. GENETIC SUSCEPTIBILITY TO PERIODONTAL
DISEASE
Periodontitis in Genetic
Syndromes and Other
Diseases
Nonsyndromic
Periodontitis

19. A. IL-1 GENE POLYMORPHISM:
• IL 1 stimulates bone resorption, inhibits collagen
synthesis, stimulates the production of other
inflammatory mediators and metalloproteinases.
• IL-1α and IL-1β are encoded, respectively, by IL1A,
IL1B genes, located near each other on the long arm
(q arm) of chromosome 2 .
1-Cytokine gene polymorphism

20. • IL-1 gene cluster is located on chromosome 2.
Cytokine gene polymorphism

21. • Meta-analyses show that at least two single nucleotide
polymorphisms: IL-1α[−889](rs1800587) and IL-
1β[+3953] (rs1143634), are associated with periodontal
inflammation. Therefore, they can be regarded as
candidate genes involved in further periodontitis risk
assessment (Brodzikowska A et al., 2019).
1-Cytokine gene polymorphism

22. B. TNF- ALPHA GENE POLYMORPHISM
• TNF triggers bone destruction by stimulating osteoclastic activity
and decreasing osteoblastic activity. TNF has been shown to be
involved in periodontitis pathogenesis.
• TNF-alpha (-308 G/A) polymorphisms might not be
associated with the risk of periodontitis, whereas the CT
genotype and the C allele of the TNF-alpha (-1031) T/C
Single nucleotide polymorphism are potential risk factors for
periodontitis in Saudi subjects (Azab E and Elfasakhany F, 2022).
1-Cytokine gene polymorphism

25. C. IL-10 GENE POLYMORPHISMS
• IL-10 gene is located on chromosome 1.
• IL-10 is a protective cytokine in periodontal disease.
• Functional disturbances in IL-10 due to genetic
polymorphisms could be detrimental to host tissue and
linked to periodontal disease susceptibility.
1-Cytokine gene polymorphism

26. OTHER CYTOKINES
• There is some preliminary evidence that genotype with
respect to the IL-2 SNP might be associated with severity
in aggressive periodontitis (Scarrel-Caminaga RM et al., 2002)
• Analysis IL-6 gene polymorphisms in Czech patients with
chronic periodontitis suggested that -572
G/Cpolymorphisms of IL-6 gene might be one of the
protective factors associated with lower susceptibility to
chronic periodontitis (Holla LI et al., 2004)

27. A. FC
R GENE POLYMORPHISMS
• .
2. Receptor and other gene polymorphisms

28. A. FC
R GENE POLYMORPHISMS
• The inflammatory cascade induced by IgG containing immune
complexes is initiated by the IgG Fc receptors on phagocytes.
Efficient clearance of IgG opzonised pathogens by phagocyte FcγR
is crucial for periodontal health. Leukocytes exhibit receptors [R]
for the constant region [Fc] of immunoglobulin molecule.
2. Receptor and other gene polymorphisms

29. A. FC
R GENE POLYMORPHISMS
2. Receptor and other gene polymorphisms

30. A. FC
R GENE POLYMORPHISMS
2. Receptor and other gene polymorphisms

31. A. FC
R GENE POLYMORPHISMS
2. Receptor and other gene polymorphisms

32. Loos BG et al., 2003

33. B. CYTOKINE AND CHEMOKINE RECEPTOR GENE
POLYMORPHISMS
2. Receptor and other gene polymorphisms

34. C. IMMUNE RECEPTOR GENE POLYMORPHISM
N-FORMYL PEPTIDE RECEPTOR POLYMORPHISMS (FPR)
• The high affinity FMLP receptor (FPR1) of phagocytic cells
interacts with bacterial FMLP and mediates chemotaxis,
degranulation, and superoxide production.
• Zhang et al., studied the prevalence of polymorphisms of the
FMLP receptor gene in localised, generalised, and grade C
periodontitis.

36. A. VITAMIN D RECEPTOR GENE (VDR) POLYMORPHISM
• Vitamin D receptor gene polymorphism has regulatory effects
on bone mineral density and bone turnover.
• Hennig et al., suggested that genetic polymorphism in Taq1
site of VDR gene might be a risk indicator for susceptibility to
Early-onset periodontal diseases (Hennig et al., 1999).
3. METABOLISM – RELATED GENE POLYMORPHISM

37. B. CALCITONIN RECEPTOR POLYMORPHISM
• Calcitonin maintains blood calcium levels and inhibits osteoclats.
• Nosaka et al., 2002 have found that patients with this polymorphism
were 20 times more likely to suffer buccal marginal bone loss than
patients who were calcitonin receptor genotype negative
3. METABOLISM – RELATED GENE
POLYMORPHISM

38. •HUMAN LEUKOCYTE ANTIGENS (HLA )GENE
POLYMORPHISM
• MHC class II molecules (HLA-DP,-DQ,-DR) are expressed on B and T
cells, macrophages and accessory cells for the presence of foreign
peptides .
• HLAs play an important role in the immune response
because they bind some of the peptides of processed
antigens and present them at the surface of
antigenpresenting cells, such as macrophages or dendritic
cells to the T-cell receptor of CD4- or CD8-positive
lymphocytes..
• .
4. Antigen – recognition related gene
polymorphism

39. • HUMAN LEUKOCYTE ANTIGENS (HLA )GENE
POLYMORPHISM
4. Antigen – recognition related gene
polymorphism

40. • HLA GENE POLYMORPHISM
• Studies have suggested that patients with the HLA-DRB1
1501- DQB1 0602 genotype may have an accelerated T
cell response to Porphyromonas. gingivalis and an
increased susceptibility to EOP in Japanese patients
(Takashiba S et al,1999).
4. Antigen – recognition related gene
polymorphism

41. A. TLR2 AND TLR4 GENE POLYMORPHISMS
• Toll-like
receptors are
signal
molecules
essential for
the cellular
response to
bacterial cell
wall
components.
5. POLYMORPHISMS IN THE INNATE IMMUNITY
RECEPTORS

42. A. TLR2 AND TLR4 GENE POLYMORPHISMS
• These polymorphisms have been correlated with
hyporesponsiveness to LPS, sepsis and infection caused by gram
negative bacteria.
• Schroeder et al., suggested that genetic variants of TLR- 4 might
act as risk factor for the development of periodontitis.(Schroeder et al., 2005)
5. POLYMORPHISMS IN THE INNATE IMMUNITY
RECEPTORS

43. B. CD 14 GENE POLYMORPHISM
• CD14 acts as
a co-receptor
(along with
the Toll-like
receptor TLR
4 for the
detection of
bacterial lipop
olysaccharide
(LPS).
5. POLYMORPHISMS IN THE INNATE IMMUNITY
RECEPTORS

44. B. CD 14 GENE POLYMORPHISM
• CD14 exists in two forms, one anchored to the membrane by
a glycosylphosphatidylinositol (GPI) tail (mCD14), the other a
soluble form (sCD14).
• Increased serum levels of sCD14 have been known to be
associated with periodontitis (Hayashi J, et al, 1999)
• There are contradictory findings from the studies of Holla et al and
Yamazaki et al. which did not find any association between CD14
genome polymorphism and chronic periodontitis(Holla et al., 2002; Yamazaki et
al, 2003)
5. POLYMORPHISMS IN THE INNATE IMMUNITY
RECEPTORS

45. A. CATHEPSIN C GENE POLYMORPHISM
• Cathepsin C is a lysosomal protease present in neutrophils and
macrophages as well as epithelial cells. Hart and co-workers, 2000,
identified and localized a gene on chromosome 11, which is
responsible for a severe form of pre-pubertal periodontitis in a
family of Jordanian descent.
• Other mutations in the CTS C gene have been linked to the
Papillon-Lefevre syndrome, a disease which is also associated with
a severe form of pre-pubertal periodontitis
6. MISCELLANEOUS GENE POLYMORPHISMS

46. B. MMP GENE POLYMORPHISM
6. MISCELLANEOUS GENE POLYMORPHISMS
SNP in gene of MMP-1 promoter region -1607 is associated with
increased risk of Grade C periodontitis.
Another study showed that three MMP polymorphisms had a small
effect on Grade A and B periodontitis.

47. C- POLYMORPHISMS IN GENES ENCODING FOR MYELOPEROXIDASE
(MPO) AND N-ACETYL TRANSFERASE (NAT-2)
• MPO and NAT2 are enzymes participating in the metabolism of
xenobiotics including arylamines from tobacco smoke. MPO is also
implicated in defence against bacterial challenge and
inflammatory tissue destruction.
6. MISCELLANEOUS GENE POLYMORPHISMS

48. C- POLYMORPHISMS IN GENES ENCODING FOR MYELOPEROXIDASE
(MPO) AND N-ACETYL TRANSFERASE (NAT-2)
• Kocher et al. and Meisel et al. conducted studies in Caucasian
population which demonstrated that the N-acetyl transferase slow
phenotype was significantly associated with severity of bone loss
(Kocher et al, 2000;Meisel et al, 2000).
6. MISCELLANEOUS GENE POLYMORPHISMS

49. D. OTHER POLYMORPHISMS
• Other polymorphisms include ACE (Angiotensin converting enzyme), ER2
(Endothelein receptor 2), IL (Interleukin) 2, IL4, IL6, IFN-GR (Interferon gamma
receptor) 1, MMP (Matrix mettaloproteinase)-1, MMP3, MMP9, MPO
(Myeloperoxidase), RAGE (Receptor for advanced glycation end products), TGF
(Transforming growth factor) β, TIMP (Tissue inhibitor of metalloproteinase) 2,
Plasminogen activation, Mannose binding lectin, Osteoprotegrin and TNFR (Tumor
necrosis factor receptor) 2 gene polymorphisms.
• Association between these polymorphisms and periodontal disease is yet to be
proved.
6. MISCELLANEOUS GENE POLYMORPHISMS

51. PERIODONTAL SUSCEPTIBILITY TEST (PST
• Currently, a genetic test is being marked for severe chronic
periodontitis, called periodontal susceptibility test (PST). It
tests for the presence of specific polymorphisms of the IL--
1a and IL-1ß genes. The genotype is determined from a
finger stick blood or saliva samples

52. PERIOPREDICT TEST I
• It examines a person’s genetic makeup to detect risk
factors for severe periodontal disease by measuring
variations in the cytokine Interleukin-1 (IL-1)
• quick, painless, and easily performed in a dentist’s office.
• A genetic sample is obtained from the mouth via a cheek
swab

53. Periodontitis in Genetic Syndromes and
Other Diseases

55. PAPILLON–LEFÈVRE SYNDROME

56. PAPILLON–LEFÈVRE SYNDROME
• Cathepsin C is a lysosomal protease present in neutrophils and
macrophages as well as epithelial cells, found on chromosome
11.
• Cathepsin C gene polymorphism lead to:
Advanced periodontal disease usually affects the primary and
secondary dentition shortly after the teeth erupt, and many
patients become edentulous while in their teens AND Palmar–
plantar keratodermas affect the palms of the hands and the
plantar surfaces of the feet.

57. HAIM–MUNK SYNDROME
Like papillon le fever mutation in
cathepsin c gene

58. CHEDIAK-HIGIASHI SYNDROME

59. CHEDIAK-HIGIASHI SYNDROME
• AR
• mutations in the lysosomal trafficking regulator gene (LYST) leading to
Prevention of lysosome fusion with phagosome, decreasing neutrophil
killing
Clinical features:
• albinism, bleeding diathesis, recurrent bacterial infections,
immunodeficiency, and neurological dysfunctions.
• It is believed that neutropenia and congenital neutrophil dysfunction in CHS
lead to bacterial invasion and rapid destruction of periodontal tissues at a
very early age.

60. NORMALLY

61. HYPOPHOSPHATASIA
• rare inherited metabolic disease
• mutations in the ALPL gene (encoding tissue-
nonspecific alkaline phosphatase) result in varying
degrees of enzyme deficiency.
• HPP manifests in a spectrum of symptoms, including
early primary tooth loss (root intact) and alveolar bone
mineralisation defects.

62. EHLER-DANLOS SYNDROME

63. EHLER-DANLOS SYNDROME
• autosomal-dominant disorder
characterized by :
• early-onset periodontitis leading to premature loss
of teeth,
• joint hypermobility, and mild skin findings

64. EHLER-DANLOS SYNDROME

65. DOWN SYNDROME
• trisomy 21 (presence of all or part of a third copy of chromosome 21)
• generalized grade C Periodontitis
• loss of teeth at an early age.
• Added to immunedeficiency, inadequate control of bacterial
plaque, deficient masticatory function, and alterations in dental
anatomy (short roots)

67. LEUKOCYTE ADHESION DEFICIENCY(LAD)
• Genetic disorder results from an inability to produce or a
failure to normally express an important cell surface integrin
(CD18), which is necessary for leukocytes to adhere to the
vessel wall at the site of infection.
• leukocytes cannot effectively adhere to the vessel wall near
the site of infection, they cannot migrate to the infection
leading to increased bacterial infection.

68. LEUKOCYTE ADHESION DEFICIENCY(LAD)
• Respiratory tract infections and sometimes otitis
media.
• Both the primary and permanent teeth are affected,
often resulting in early tooth loss.