The Effect of Single Nucleotide Polymorphisms (SNPs) in Toll-Like Receptors -2, -4, -9, and CD14 Genes in an African-American Population with Chronic Periodontitis

AIM: to determine if a relationship exists between TLR-2, TLR-4, TLR-9, or CD14 polymorphisms and risk for developing chronic periodontal disease in an African-American population. This is the first study conducted to determine role of SNPs in TLR genes and CD14 gene in a periodontally-diseased Afr...

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Main Author: Maughan, Willard
Format: Others
Published: VCU Scholars Compass 2009
Subjects:
Online Access:http://scholarscompass.vcu.edu/etd/1844
http://scholarscompass.vcu.edu/cgi/viewcontent.cgi?article=2843&context=etd
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spelling ndltd-vcu.edu-oai-scholarscompass.vcu.edu-etd-28432017-03-17T08:31:10Z The Effect of Single Nucleotide Polymorphisms (SNPs) in Toll-Like Receptors -2, -4, -9, and CD14 Genes in an African-American Population with Chronic Periodontitis Maughan, Willard AIM: to determine if a relationship exists between TLR-2, TLR-4, TLR-9, or CD14 polymorphisms and risk for developing chronic periodontal disease in an African-American population. This is the first study conducted to determine role of SNPs in TLR genes and CD14 gene in a periodontally-diseased African-American population. Additionally, this is the first study to assess the role of TLR-9 polymorphism in periodontitis patients. METHODS: A total of 130 subjects were involved in the study. The chronic periodontitis (CP) group contained 73 subjects, and the healthy control (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 the periodontally diseased group versus the control 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 the control 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 CD14 polymorphism. CONCLUSION: Based on findings of this study, homozygocity for the T allele of TLR 9 polymorphism was related to chronic periodontal disease susceptibility in African Americans. Additionally, presence of the C allele at TLR-9 appeared to confer resistance to periodontal destruction. Our results showed that specific SNPs in TLR-2, -4 and CD14 genes are not related to periodontitis in African Americans. 2009-06-03T07:00:00Z text application/pdf http://scholarscompass.vcu.edu/etd/1844 http://scholarscompass.vcu.edu/cgi/viewcontent.cgi?article=2843&amp;context=etd © The Author Theses and Dissertations VCU Scholars Compass periodontitis toll-like receptor tlr-2 tlr-4 tlr-9 cd14 innate immunity Dentistry Medicine and Health Sciences Periodontics and Periodontology
collection NDLTD
format Others
sources NDLTD
topic periodontitis
toll-like receptor
tlr-2
tlr-4
tlr-9
cd14
innate immunity
Dentistry
Medicine and Health Sciences
Periodontics and Periodontology
spellingShingle periodontitis
toll-like receptor
tlr-2
tlr-4
tlr-9
cd14
innate immunity
Dentistry
Medicine and Health Sciences
Periodontics and Periodontology
Maughan, Willard
The Effect of Single Nucleotide Polymorphisms (SNPs) in Toll-Like Receptors -2, -4, -9, and CD14 Genes in an African-American Population with Chronic Periodontitis
description AIM: to determine if a relationship exists between TLR-2, TLR-4, TLR-9, or CD14 polymorphisms and risk for developing chronic periodontal disease in an African-American population. This is the first study conducted to determine role of SNPs in TLR genes and CD14 gene in a periodontally-diseased African-American population. Additionally, this is the first study to assess the role of TLR-9 polymorphism in periodontitis patients. METHODS: A total of 130 subjects were involved in the study. The chronic periodontitis (CP) group contained 73 subjects, and the healthy control (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 the periodontally diseased group versus the control 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 the control 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 CD14 polymorphism. CONCLUSION: Based on findings of this study, homozygocity for the T allele of TLR 9 polymorphism was related to chronic periodontal disease susceptibility in African Americans. Additionally, presence of the C allele at TLR-9 appeared to confer resistance to periodontal destruction. Our results showed that specific SNPs in TLR-2, -4 and CD14 genes are not related to periodontitis in African Americans.
author Maughan, Willard
author_facet Maughan, Willard
author_sort Maughan, Willard
title The Effect of Single Nucleotide Polymorphisms (SNPs) in Toll-Like Receptors -2, -4, -9, and CD14 Genes in an African-American Population with Chronic Periodontitis
title_short The Effect of Single Nucleotide Polymorphisms (SNPs) in Toll-Like Receptors -2, -4, -9, and CD14 Genes in an African-American Population with Chronic Periodontitis
title_full The Effect of Single Nucleotide Polymorphisms (SNPs) in Toll-Like Receptors -2, -4, -9, and CD14 Genes in an African-American Population with Chronic Periodontitis
title_fullStr The Effect of Single Nucleotide Polymorphisms (SNPs) in Toll-Like Receptors -2, -4, -9, and CD14 Genes in an African-American Population with Chronic Periodontitis
title_full_unstemmed The Effect of Single Nucleotide Polymorphisms (SNPs) in Toll-Like Receptors -2, -4, -9, and CD14 Genes in an African-American Population with Chronic Periodontitis
title_sort effect of single nucleotide polymorphisms (snps) in toll-like receptors -2, -4, -9, and cd14 genes in an african-american population with chronic periodontitis
publisher VCU Scholars Compass
publishDate 2009
url http://scholarscompass.vcu.edu/etd/1844
http://scholarscompass.vcu.edu/cgi/viewcontent.cgi?article=2843&amp;context=etd
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