GenF Periodontal Disease Flashcards
What is meant by heritable risk of periodontal disease?
Although bacteria are considered to be the cause of periodontitis, disease may only be manifest in a susceptible host OR Genetic background is one factor that can contribute to overall risk for disease
What does the twin model teach us about attachment loss?
In monozygotic twins, the difference in attachment loss is because of environment. In dizygotic twins, the difference is due to the environment and half the genes
What is used to test whether a genetic variant (allele, gene frequency, haplotype) is different for 2 groups (usually diseased subjects and healthy controls)?
Association studies
True or false: A person carrying one or two copies of a high-risk variant is at increased risk of developing the associated disease or having the associated trait?
True
True or False: If an association is present, a particular allele, genotype or haplotype of a polymorphism or polymorphism(s) will be seen more often than expected by chance in an individual carrying the trait?
True
Activation of macrophages by bacterial LPS to produce inflammatory cytokines: innate immunity is an example of innate or adaptive immunity?
Innate
Enhanced activation of macrophages by T-cell derived inflmmatory cytokine INF-gamma is an example of innate or adaptive immunity?
Immunity
What inflammatory cytokines and lipid mediators regulate differentiation of osteoclasts?
Interleukin-1 (IL-1) Interleukin-6 (IL-6) Tumor necrosis factor-alpha (TNF-a) Interferon gamma (IFN-g) Prostaglandin E2 (PGE2) RANK ligand (RANK-L)
What are three ways innate immunity can lead to periodontitis?
- De-activating Fc receptor down regulating pro-inflammatory response
- Activating Fc receptor promoting pro-inflammatory response
- Pro-inflammatory cytokine
What is one way that acquired immunity can lead to periodontitis?
Type 1 receptor for interferon gamme on macrophages
The polymorphis IL-1A (+4845) and IL-1B (+3954) affects what gene?
Interleukin-1 gene
The polymorphism TNF-alpha-308 allele 1 affects what gene?
TNF-alpha gene
The TNF-beta Ncol, ET-1 gene and ACE gene insertion/deletion polymorphism affects what gene?
Lymphotoxin alpha (TNF-beta) enothelin-1 (ET-1), and angiotensin-converting enzyme (ACE) genes
The Fc gammaRIIIb-NA2 allotype polymorphism affects what gene?
Fc receptor polymorphism
The NAT2 polymorphism affects what gene?
N-acetyltransferase polymorphism
The VDR Apa1 polymorphism affects what gene?
Vitamin D Receptor
Which pro-inflammatory, multifunctional cytokine enables ingress of inflammatory cells into sites of infection and promotes bone resorption?
IL-1
Which salivary diagnostic test identifies the type and concentration of specific perio-pathogenic bacteria that are known to cause periodontal disease?
MyPerioPath
Which test identifies individual genetic susceptibility to periodontal disease and enables the clinician to establish which patient are at increased risk of more severe periodontal infections due to an exaggerated immune response?
MyPerioID PST
Who should be tested (for MyPerioID PST)?
- Patients with a family history of periodontal disease
- Patients with compromised immune systems
- Patients who have received therapy but continue with disease activity
A positive reading for MyPerioID PST means the patient’s risk of periodontal disease is increased by waht amount?
5-7 times
The genes tested by the PST test are located on what chromosome?
2
Homozygotes for the IL-1 gene that controls IL-1B concentrates have how many times the normal level of IL-B1?
Four times
In northern european homozygotes for the IL-1 gene their risk for severe periodontitis by what amount?
19 times
What are the two allelic forms of Fc(gamma)RIIIb on PMNs?
NA1/NA1 and NA2/NA2
What type of phagocytic capacity for IgG1 and IgG3 do PMNs have with NA1/NA1?
High
What type of phagocytic capacity for IgG1 and IgG3 do PMNs have with NA2/NA2?
Low
What are the relative risks for the various combinations of NA1 and NA2?
NA1/NA1 = about 1.7 NA1/NA2 = about 4.3 NA2/NA2 = about 4.5
What are some problems with studies of genetic polymorphisms in periodontitis?
- Small cohorts (high potential for false positive and negative results)
- Genotype and allele frequencies vary between ethnic populations: not consistent risk factors
- Phenotype difficult (i.e. AgP vs CP, extent, severity patterns)
What are some lessons from studies of genetic polymorphisms?
- Applicability of results to subject populations and diagnostic groups not uniform
- Increased information likely if examine multiple interacting or additive genes or moderate risk
- Indirect association: risk may only apparent with exposure to specific environmental risk factor
What gene is associated with coronary heart disease (CHD) and periodontitis?
9p21.3
What does ANRIL stand for?
Antisense non-coding RNA in the INK4 locus
What are some characteristics of Chromosome 9p21 “disease hot spot”?
- Strongest genetic suceptibility locs of CDV: independent risk factor
- Also linked to type 2 diabetes, Alzheimers disease, glaucoma, endometriosis and periodontitis, and several cancers
- Disease-associated haplotype block, with the genes
- Most of the disease-associated polymorphisms have been associated with the expression of ANRIL
What is a single-stranded RNA that is complementary to a mRNA strand transcribed within a cell?
Antisense RNA
How may antisense RNA inhibity translation of mRNA?
By pairing to it
