FREQUENCY OF TLR-2, 4, 9 AND CD14 POLYMORPHISMS IN AGGRESSIVE PERIODONTITIS POPULATION IN AFRICAN-AMERICANS
Aim: The aim of this study is to determine the frequency of single nucleotide polymorphisms (SNPs) in various pattern recognition receptor (PRR) genes, including Toll like receptors (TLR) -2, -4, -9, and CD14 in chronic (CP), localized (LAP) and generalized aggressive (GAP) periodontitis and periodo...
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ndltd-vcu.edu-oai-scholarscompass.vcu.edu-etd-28442017-03-17T08:30:01Z FREQUENCY OF TLR-2, 4, 9 AND CD14 POLYMORPHISMS IN AGGRESSIVE PERIODONTITIS POPULATION IN AFRICAN-AMERICANS Chou, Melanie Aim: The aim of this study is to determine the frequency of single nucleotide polymorphisms (SNPs) in various pattern recognition receptor (PRR) genes, including Toll like receptors (TLR) -2, -4, -9, and CD14 in chronic (CP), localized (LAP) and generalized aggressive (GAP) periodontitis and periodontally healthy (NP) patients in an African American population. Methods: A total of 205 subjects were involved in the study. The LAP group consists of 25 subjects, the GAP group 50 subjects, the CP group 73 subjects and the NP group 57subjects. Genotyping was performed in TLR2 (G2408A), TLR4 (A896G),TLR9 (T1486C) and CD14 (C260T) genes by TaqMan® allelic discrimination using Assay-by-DesignSM SNP Genotyping Assays (Applied Biosystems). Accuracy of genotyping was confirmed by known DNA samples of each genotype and by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) analyses on selected samples. Fisher’s exact test and chi-square analyses were performed to compare genotype and allele frequencies. Within disease groups, we investigated whether SNPs were related to disease severity by step-wise logistic regression adjusted for age, gender, and smoking status. Results: There was a significant difference in the distribution of specific TLR9 (T1486C) genotypes between diseased-groups versus reference group. Expression of TT genotype was more prevelant in periodontally-diseased individuals compared to periodontally-healthy subjects (p<0.0001) whereas individuals expressing C allele of the TLR9 SNP (CC&CT) were more frequently found in healthy group after adjusting for age, gender, and smoking status (p<0.0001) There was no statistically significant difference in the distribution of genotypes between groups for any other TLRs or CD 14 polymorphism. Conclusion: Based on findings of this study, homozygocity for the T allele of TLR 9 polymorphism was related to the periodontal disease susceptibility in African Americans. Additionally, presence of C allele at TLR-9 appeared to confer resistance to periodontal destruction. Our results showed that specific SNPs in TLR-2, -4 and CD 14 genes are not related to periodontitis in African Americans. However, low copy number of certain alleles warrants further investigations with increased sample size to explore the role of SNPs in periodontal disease. This study was supported by the Alexander Fellowship. 2009-06-03T07:00:00Z text application/pdf http://scholarscompass.vcu.edu/etd/1845 http://scholarscompass.vcu.edu/cgi/viewcontent.cgi?article=2844&context=etd © The Author Theses and Dissertations VCU Scholars Compass TLR 2 TLR 4 TLR 9 aggressive periodontitis innate immunity Dentistry Medicine and Health Sciences Periodontics and Periodontology |
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TLR 2 TLR 4 TLR 9 aggressive periodontitis innate immunity Dentistry Medicine and Health Sciences Periodontics and Periodontology |
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TLR 2 TLR 4 TLR 9 aggressive periodontitis innate immunity Dentistry Medicine and Health Sciences Periodontics and Periodontology Chou, Melanie FREQUENCY OF TLR-2, 4, 9 AND CD14 POLYMORPHISMS IN AGGRESSIVE PERIODONTITIS POPULATION IN AFRICAN-AMERICANS |
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Aim: The aim of this study is to determine the frequency of single nucleotide polymorphisms (SNPs) in various pattern recognition receptor (PRR) genes, including Toll like receptors (TLR) -2, -4, -9, and CD14 in chronic (CP), localized (LAP) and generalized aggressive (GAP) periodontitis and periodontally healthy (NP) patients in an African American population. Methods: A total of 205 subjects were involved in the study. The LAP group consists of 25 subjects, the GAP group 50 subjects, the CP group 73 subjects and the NP group 57subjects. Genotyping was performed in TLR2 (G2408A), TLR4 (A896G),TLR9 (T1486C) and CD14 (C260T) genes by TaqMan® allelic discrimination using Assay-by-DesignSM SNP Genotyping Assays (Applied Biosystems). Accuracy of genotyping was confirmed by known DNA samples of each genotype and by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) analyses on selected samples. Fisher’s exact test and chi-square analyses were performed to compare genotype and allele frequencies. Within disease groups, we investigated whether SNPs were related to disease severity by step-wise logistic regression adjusted for age, gender, and smoking status. Results: There was a significant difference in the distribution of specific TLR9 (T1486C) genotypes between diseased-groups versus reference group. Expression of TT genotype was more prevelant in periodontally-diseased individuals compared to periodontally-healthy subjects (p<0.0001) whereas individuals expressing C allele of the TLR9 SNP (CC&CT) were more frequently found in healthy group after adjusting for age, gender, and smoking status (p<0.0001) There was no statistically significant difference in the distribution of genotypes between groups for any other TLRs or CD 14 polymorphism. Conclusion: Based on findings of this study, homozygocity for the T allele of TLR 9 polymorphism was related to the periodontal disease susceptibility in African Americans. Additionally, presence of C allele at TLR-9 appeared to confer resistance to periodontal destruction. Our results showed that specific SNPs in TLR-2, -4 and CD 14 genes are not related to periodontitis in African Americans. However, low copy number of certain alleles warrants further investigations with increased sample size to explore the role of SNPs in periodontal disease. This study was supported by the Alexander Fellowship. |
author |
Chou, Melanie |
author_facet |
Chou, Melanie |
author_sort |
Chou, Melanie |
title |
FREQUENCY OF TLR-2, 4, 9 AND CD14 POLYMORPHISMS IN AGGRESSIVE PERIODONTITIS POPULATION IN AFRICAN-AMERICANS |
title_short |
FREQUENCY OF TLR-2, 4, 9 AND CD14 POLYMORPHISMS IN AGGRESSIVE PERIODONTITIS POPULATION IN AFRICAN-AMERICANS |
title_full |
FREQUENCY OF TLR-2, 4, 9 AND CD14 POLYMORPHISMS IN AGGRESSIVE PERIODONTITIS POPULATION IN AFRICAN-AMERICANS |
title_fullStr |
FREQUENCY OF TLR-2, 4, 9 AND CD14 POLYMORPHISMS IN AGGRESSIVE PERIODONTITIS POPULATION IN AFRICAN-AMERICANS |
title_full_unstemmed |
FREQUENCY OF TLR-2, 4, 9 AND CD14 POLYMORPHISMS IN AGGRESSIVE PERIODONTITIS POPULATION IN AFRICAN-AMERICANS |
title_sort |
frequency of tlr-2, 4, 9 and cd14 polymorphisms in aggressive periodontitis population in african-americans |
publisher |
VCU Scholars Compass |
publishDate |
2009 |
url |
http://scholarscompass.vcu.edu/etd/1845 http://scholarscompass.vcu.edu/cgi/viewcontent.cgi?article=2844&context=etd |
work_keys_str_mv |
AT choumelanie frequencyoftlr249andcd14polymorphismsinaggressiveperiodontitispopulationinafricanamericans |
_version_ |
1718428404598964224 |