Dataset Information

Comparative salivary proteomics analysis of children with and without dental caries using the iTRAQ/MRM approach

ABSTRACT: In this study, unstimulated saliva samples were collected from 30 children (age 10-12 years) with no dental caries (NDC, n=10), low dental caries (LDC, n=10), and high dental caries (HDC, n=10). Salivary proteins were extracted, reduced, alkylated, trypsin digested and labeled with isobaric tags for relative and absolute quantitation (iTRAQ), and then they were analyzed with GO annotation, biological pathway analysis, hierarchical clustering analysis, and protein-protein interaction analysis. Targeted verifications were then performed using multiple reaction monitoring mass spectrometry (MRM-MS).

ORGANISM(S): Homo Sapiens

SUBMITTER: Linglin Zhang

PROVIDER: PXD008488 | iProX | Tue Dec 19 00:00:00 GMT 2017

REPOSITORIES: iProX

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Comparative salivary proteomics analysis of children with and without dental caries using the iTRAQ/MRM approach.

Wang Kun K Wang Yufei Y Wang Xiuqing X Ren Qian Q Han Sili S Ding Longjiang L Li Zhongcheng Z Zhou Xuedong X Li Wei W Zhang Linglin L

Journal of translational medicine 20180119 1

<h4>Background</h4>Dental caries is a major worldwide oral disease afflicting a large proportion of children. As an important host factor of caries susceptibility, saliva plays a significant role in the occurrence and development of caries. The aim of the present study was to characterize the healthy and cariogenic salivary proteome and determine the changes in salivary protein expression of children with varying degrees of active caries, also to establish salivary proteome profiles with a poten ...[more]

PMID: 29351798

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Project description:Background. Hematopoietic cell transplantation (HCT) is a potentially curative therapy for a wide range of pediatric malignant and nonmalignant diseases. However, complications, including blood stream infection (BSI) remain a major cause of morbidity and mortality. While certain bacteria that are abundant in the oral microbiome, such as S. mitis, can cause BSI, the role of the oral microbial community in the etiology of BSI is not well understood. The finding that the use of xylitol wipes, which specifically targets the cariogenic bacteria S. mutans is associated with reduced BSI in pediatric patients, lead us to investigate dental caries as a risk factor for BSI. Methods. A total of 41 pediatric patients admitted for allogenic or autologous HCT, age 8 months to 25 years, were enrolled. Subjects with high dental caries risk were identified as those who had dental restorations completed within 2 months of admission for transplant, or who had untreated decay. Fisher’s exact test was used to determine if there was a significant association between caries risk and BSI. Dental plaque and saliva were collected on a cotton swab from a subset of 4 high caries risk (HCR) and 4 low caries risk (LCR) children following pretransplant conditioning. 16SrRNA sequencing was used to compare the microbiome of HCR and LCR subjects and to identify microbes that were significantly different between the 2 groups. Results. There was a statistically significant association between caries risk and BSI (p<0.035) (Fisher’s exact test). Multivariate logistic regression analysis showed children in the high dental caries risk group were 21.39 times more likely to have BSI, with no significant effect of age or mucositis severity. HCR subjects showed significantly reduced microbial alpha diversity as compared to LCR subjects. LEfse metagenomic analyses, showed the oral microbiome in HCR children enriched in order Lactobacillales. This order includes Streptococcus and Lactobacillus, both which contain bacteria primarily associated with dental caries. Discussion. These findings support the possibility that the cariogenic microbiome can enhance the risk of BSI in pediatric populations. Future metagenomic analyses to measure microbial differences at, before, and after conditioning related to caries risk, may further unravel the complex relationship between the oral microbiome, and whether it affects health outcomes such as BSI.

Project description:Dental caries (also known as tooth decay) remains the most common chronic disease of childhood, five times more common than asthma and seven times more common than environmental allergies, with more than 40% of children exhibiting caries when they enter kindergarten. In 2005, it was estimated that dental health care costs were approximately $84 billion, of which 60% or about $50 billion were related to treatment of dental caries. Although overall caries prevalence has declined over the last 40 years, dental caries in the primary dentition and mean caries rates in children ages 2-11 has increased markedly over the past 12 years. Childhood caries is a serious public health issue because of associated health problems and because disparities in oral health have led to substantially higher average disease prevalence among children in poverty and in under-served racial and ethnic groups. These issues are of such concern that in 2005, the American Academy of Pediatrics made children's oral health one of their top areas of focus, as it is for the majority of the NIDCR "Disparities Centers". The etiology of dental caries has been studied for many years. Multiple factors contribute to a person's risk for caries, including: 1) environmental factors such as diet, oral hygiene, fluoride exposure and the level of colonization of cariogenic bacteria and 2) host factors such as salivary flow, salivary buffering capacity, position of teeth relative to each other, surface characteristics of tooth enamel and depth of occlusal fissures on posterior teeth. In spite of all that is known about this disease, there are still individuals who appear to be more susceptible to caries and those who are extremely resistant, regardless of the environmental risk factors to which they are exposed, implying that genetic factors also play an important role in caries etiology. This conclusion is supported by studies in both humans and animals, with the most compelling evidence coming from studies of twins reared apart in which investigators found significant resemblance within monozygotic (MZ) but not dizygotic (DZ) twin pairs for percentage of teeth and surfaces restored or carious and estimated the genetic contribution to caries as 40%. Other recent studies of twins reared together estimated the heritability for caries, adjusted for age and gender, as ranging from 45-64%. Despite the strong evidence of a genetic component to risk for dental caries, there have been only a few studies of candidate genes in caries, and no published genome-wide scans. A comprehensive genome wide search is the only approach that will allow us to identify those genetic regions likely to harbor genes increasing the risk for dental caries, and eventually to identify the etiologic genes and to explore the interaction of those genes with microbiological, dietary, fluoride, and behavioral factors that are known to be associated with caries risk and progression. Therefore, the goal of this study is to perform genome-wide association (GWA) studies of dental caries with a large panel of SNP's (610,000) in families and individuals ascertained through multiple US sites (University of Pittsburgh and University of Iowa). The v2 release of this study includes 96 additional individuals who were genotyped with the CCDG: Dental Caries and CL/P in Guatemala project (dbGaP accession number <a href="./study.cgi?study_id=phs000440">phs000440</a>) to augment the data initially presented here. These subjects were genotyped on the Illumina 610 platform to make their data comparable. This study is part of the Gene Environment Association Studies initiative (GENEVA, <a href="http://www.genevastudy.org" target="_blank">http://www.genevastudy.org</a>), which was developed through the trans-NIH Genes, Environment, and Health Initiative (GEI). The overarching goal is to identify novel genetic factors that contribute to dental caries through large-scale genome-wide association studies of well-characterized families and individuals at multiple sites in the U.S. Genotyping was performed at the Johns Hopkins University Center for Inherited Disease Research (CIDR). The study was supported by the National Institute of Dental and Craniofacial Research (NIDCR, U01-DE018903). Data cleaning and harmonization were done at the GEI-funded GENEVA Coordinating Center at the University of Washington.

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Comparative salivary proteomics analysis of children with and without dental caries using the iTRAQ/MRM approach

Publications

Comparative salivary proteomics analysis of children with and without dental caries using the iTRAQ/MRM approach.

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