Exploring the genomic basis of early childhood caries: a pilot study

Objective: A genetic component in early childhood caries (ECC) is theorized, but no genome-wide investigations of ECC have been conducted. This pilot study is part of a long-term research program aimed to: (1) determine the proportion of ECC variance attributable to the human genome and (2) identify ECC-associated genetic loci. Methods: The study's community-based sample comprised 212 children (mean age=39 months; range = 30–52 months; males = 55%; Hispanic/Latino = 35%, African-American = 32%; American Academy of Pediatric Dentistry definition of ECC prevalence = 38%). Approximately 2.4 million single nucleotide polymorphisms (SNPs) were genotyped using DNA purified from saliva. A P < 5 × 10−8 criterion was used for genome-wide significance. SNPs with P < 5 × 10−5 were followed-up in three independent cohorts of 921 preschool-age children with similar ECC prevalence. Results: SNPs with minor allele frequency ≥5% explained 52% (standard error = 54%) of ECC variance (one-sided P = 0.03). Unsurprisingly, given the pilot's small sample size, no genome-wide significant associations were found. An intergenic locus on 4q32 (rs4690994) displayed the strongest association with ECC [P = 2.3 × 10−6; odds ratio (OR) = 3.5; 95% confidence interval (CI) = 2.1–5.9]. Thirteen loci with suggestive associations were followed-up – none showed evidence of association in the replication samples. Conclusion: This study's findings support a heritable component of ECC and demonstrate the feasibility of conducting genomics studies among preschool-age children

Genes and Their Effects on Dental Caries May Differ between Primary and Permanent Dentitions

The importance of genetic factors in the genesis of dental caries of both primary and permanent dentitions is well established; however, the degree to which genes contribute to the development of dental caries, and whether these genes differ between primary and permanent dentitions, is largely unknown. Using family-based likelihood methods, we assessed the heritability of caries-related phenotypes for both children and adults in 2,600 participants from 740 families. We found that caries phenotypes in the primary dentition were highly heritable, with genes accounting for 54–70% of variation in caries scores. The heritability of caries scores in the permanent dentition was also substantial (35–55%, all p < 0.01), although this was lower than analogous phenotypes in the primary dentition. Assessment of the genetic correlation between primary and permanent caries scores indicated that 18% of the covariation in these traits was due to common genetic factors (p < 0.01). Therefore, dental caries in primary and permanent teeth may be partly attributable to different suites of genes or genes with differential effects. Sex and age explained much of the phenotypic variation in permanent, but not primary, dentition. Further, including pre-cavitated white-spot lesions in the phenotype definition substantially increased the heritability estimates for dental caries. In conclusion, our results show that dental caries are heritable, and suggest that genes affecting susceptibility to caries in the primary dentition may differ from those in permanent teeth. Moreover, metrics for quantifying caries that incorporate white-spot lesions may serve as better phenotypes in genetic studies of the causes of tooth decay

Oral diseases: a global public health challenge

Oral diseases are among the most prevalent diseases globally and have serious health and economic burdens, greatly reducing quality of life for those affected. The most prevalent and consequential oral diseases globally are dental caries (tooth decay), periodontal disease, tooth loss, and cancers of the lips and oral cavity. In this first of two papers in a Series on oral health, we describe the scope of the global oral disease epidemic, its origins in terms of social and commercial determinants, and its costs in terms of population wellbeing and societal impact. Although oral diseases are largely preventable, they persist with high prevalence, reflecting widespread social and economic inequalities and inadequate funding for prevention and treatment, particularly in low-income and middle-income countries (LMICs). As with most non-communicable diseases (NCDs), oral conditions are chronic and strongly socially patterned. Children living in poverty, socially marginalised groups, and older people are the most affected by oral diseases, and have poor access to dental care. In many LMICs, oral diseases remain largely untreated because the treatment costs exceed available resources. The personal consequences of chronic untreated oral diseases are often severe and can include unremitting pain, sepsis, reduced quality of life, lost school days, disruption to family life, and decreased work productivity. The costs of treating oral diseases impose large economic burdens to families and health-care systems. Oral diseases are undoubtedly a global public health problem, with particular concern over their rising prevalence in many LMICs linked to wider social, economic, and commercial changes. By describing the extent and consequences of oral diseases, their social and commercial determinants, and their ongoing neglect in global health policy, we aim to highlight the urgent need to address oral diseases among other NCDs as a global health priority

Ending the neglect of global oral health: time for radical action

Oral diseases are a major global public health problem affecting over 3·5 billion people. However, dentistry has so far been unable to tackle this problem. A fundamentally different approach is now needed. In this second of two papers in a Series on oral health, we present a critique of dentistry, highlighting its key limitations and the urgent need for system reform. In high-income countries, the current treatment-dominated, increasingly high-technology, interventionist, and specialised approach is not tackling the underlying causes of disease and is not addressing inequalities in oral health. In low-income and middle-income countries (LMICs), the limitations of so-called westernised dentistry are at their most acute; dentistry is often unavailable, unaffordable, and inappropriate for the majority of these populations, but particularly the rural poor. Rather than being isolated and separated from the mainstream health-care system, dentistry needs to be more integrated, in particular with primary care services. The global drive for universal health coverage provides an ideal opportunity for this integration. Dental care systems should focus more on promoting and maintaining oral health and achieving greater oral health equity. Sugar, alcohol, and tobacco consumption, and their underlying social and commercial determinants, are common risk factors shared with a range of other non-communicable diseases (NCDs). Coherent and comprehensive regulation and legislation are needed to tackle these shared risk factors. In this Series paper, we focus on the need to reduce sugar consumption and describe how this can be achieved through the adoption of a range of upstream policies designed to combat the corporate strategies used by the global sugar industry to promote sugar consumption and profits. At present, the sugar industry is influencing dental research, oral health policy, and professional organisations through its well developed corporate strategies. The development of clearer and more transparent conflict of interest policies and procedures to limit and clarify the influence of the sugar industry on research, policy, and practice is needed. Combating the commercial determinants of oral diseases and other NCDs should be a major policy priority

An Assessment of Survival Rates and Within-patient Clustering of Failures for Endosseous Oral Implants

This study examined endosseous cylinder implant survival, defined as the unqualified presence of the implant in the mouth at the end of the observation period, in 598 consecutive VA patients, with a total of 2098 implants. Data were taken from the Department of Veterans Affairs (VA) Dental Implant Registry, which has maintained longitudinal data on the survival of individual dental implants in VA patients since 1987. The maximum time of observation in any one patient was 2040 days (5.6 yr). Survival analysis by use of life-table methods was carried out on both an implant- and a patient-specific basis. Implant cases were accrued randomly, and therefore a random censoring model was used. A correlated binomial model was used for assessment of the degree of within-patient clustering of implant removals. Results showed that the implant-specific survival rate during the longest time interval (5.6 yr) was 89.9%; the patient-specific implant survival rate during the same time was 78.2%. Among implants which were removed, the mean time to removal was 292 days. The hazard function, which describes the probability of implant loss as a function of time, decreased steadily throughout the observation period. The correlated binomial model suggested a clustering of removals within patients with multiple implants (p = 0.11, p = 0.0001). The odds of having a second implant removed were 1.3 times greater if the patient had already had one implant removed. This study suggests that when implants fail, they do so soon after placement, and the likelihood of failure decreases steadily from implantation through the first five years post-surgery. These findings also suggest the existence of systemic factors which affect the survival of all implants within a given patient and may lead to multiple implant failures. Identification of these systemic factors may lead to improvements in patient selection and increases in the success rates for oral implants. Finally, results show that pure titanium implants had better short-term survival rates, but worse long-term survival rates, when compared with implants that had some other form of surface coating.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/67808/2/10.1177_00220345930720010201.pd

IL-1RN gene polymorphism is associated with peri-implantitis

Objectives: Interleukin (IL)-1 alpha, IL-1 beta and their natural specific inhibitor IL-1 receptor antagonist (IL-1ra) play a key role in the regulation of the inflammatory response in periodontal tissues. Polymorphisms in the IL-1 gene cluster have been associated with severe adult periodontitis. We aimed to investigate the IL-1 gene cluster polymorphisms in patients with peri-implantitis. Material and methods: The study included 120 North Caucasian individuals. A total of 71 patients (mean age 68 years, 76% smokers) demonstrating peri-implantitis at one or more implants as evidenced by bleeding and/or pus on probing and bone loss amounting to > 3 threads on Branemark implants and 49 controls (mean age 66 years, 45% smokers) with clinical healthy mucosa and no bone loss around the implants were recruited for the study. The titanium implants, ad modum Branemark, had been in function for at least 2 years. Mouthwash samples were collected and used for genotyping of the bi-allelic polymorphisms IL-1A(-889), IL-1B(+3953), IL-1B(-511) and a variable number of tandem repeat IL-1RN gene polymorphisms using PCR technique. Results: Significant differences were found in the carriage rate of allele 2 in the IL-1RN gene between peri-implantitis patients and controls (56.5% vs. 33.3%, respectively; odds ratios (OR) 2.6; 95% confidence interval (CI) 1.2-5.6; P=0.015). Logistic regression analysis taking smoking, gender and age into account confirmed the association between the IL-1RN allele 2 carriers and peri-implantitis (OR 3; 95% CI 1.2-7.6; P=0.02). Conclusions: Our results provide evidence that IL-1RN gene polymorphism is associated with peri-implantitis and may represent a risk factor for this disease