DNA methylation and its potential roles in common oral diseases.

Oral diseases are among the most common diseases worldwide and are associated with systemic illnesses, and the rising occurrence of oral diseases significantly impacts the quality of life for many individuals. It is crucial to detect and treat these conditions early to prevent them from advancing. DNA methylation is a fundamental epigenetic process that contributes to a variety of diseases including various oral diseases. Taking advantage of its reversibility, DNA methylation becomes a viable therapeutic target by regulating various cellular processes. Understanding the potential role of this DNA alteration in oral diseases can provide significant advances and more opportunities for diagnosis and therapy. This article will review the biology of DNA methylation, and then mainly discuss the key findings on DNA methylation in oral cancer, periodontitis, endodontic disease, oral mucosal disease, and clefts of the lip and/or palate in the background of studies on global DNA methylation and gene-specific DNA methylation.

Gene sequencing applications to combat oral-cavity related disorders: a systematic review with meta-analysis.

Gene sequencing (GS) has numerous applications in combatting oral-cavity related disorders, including identifying genetic risk factors for diseases, developing targeted therapies, and improving diagnostic methods. It can help identify specific genetic mutations or variations that increase the risk of developing oral-cavity related disorders, such as oral cancer, periodontal disease, and cleft lip and palate. By the means of the following investigation, our primary objective was to assess the impact of GS technique in diagnosing and potentially treating diseases of the oral cavity by the means of a systematic review and meta-analysis. We commenced by defining the terms "gene sequencing," "oral cavity," and "disorders" as the important elements in our investigation's subject. Next, relevant databases like PubMed, Scopus, Embase, Web of Science, and Google Scholar were searched using keywords and synonyms for each concept, such as "genomic sequencing," "DNA sequencing," "oral health," "oral diseases," "dental caries," "periodontal disease," "oral cancer," and "salivary gland disorders." We combined several search terms, such as "gene sequencing AND oral disorders AND periodontal disease" or "oral cancer OR genomic sequencing," to further hone your search results using Boolean operators like "AND" and "OR." The oral cavity analysis obtained by CS in the selected articles revealed that most of the disorders were, in fact, a direct causal event influenced by the oral microbiome. Moreover, each sampled oral cavity evidenced a different microbial community, which predicted the precipitation of benign as well as malignant conditions, though not on a definitive basis. In the last ten years, genomic sequencing had advanced remarkably as majority of our selected studies observed, making it possible to diagnose and treat a variety of oral and maxillofacial disorders, including cancer. It was also used to ascertain a person's genetic make-up as well as to spot numerous genetic abnormalities that can predispose individuals to diseases. Understanding the different sequencing techniques and the resulting genetic anomalies may help with their clinical application and lead to an improvement in illness diagnosis and prognosis as a whole in the field of dentistry.

[Application status and prospect of genetic counseling in stomatology in China].

Oral genetic diseases and rare diseases are special oral diseases with low prevalence, complex clinical characteristics and serious condition. In addition to regular oral diagnosis and treatment, multidisciplinary diagnosis and treatment including genetic counseling should also be carried out for such diseases. This article reviews the basic content of genetic counseling, the current application status of genetic counseling in the field of stomatology in China and the problems faced, such as the lack of genetic counseling personnel and the popularization of genetic counseling knowledge. Aims to promote the application of genetic counseling in dental practice in the future, it is proposed to carry out genetic training for stomatologists, promote the integration of medical genetic expertise and oral knowledge, as well as discipline cooperation, and strengthen the standardization of genetic counseling for oral diseases.

Comparison of biomarker expression in oral lichen planus and oral lichenoid lesions.

BACKGROUND: Oral lichen planus (OLP) and oral lichenoid lesions (OLL) comprise a group of oral mucosal disorders that have similar clinical and histological features. OBJECTIVES: To compare the levels of investigated biomarkers in biopsied OLP and OLL, and to determine the pattern of biomarkers, which could be useful for the biological characterization of these 2 disorders. MATERIAL AND METHODS: A total of 56 biopsy specimens in 2 groups were analyzed in this study. One group consisted of 25 idiopathic OLP lesions, and the other included 31 OLL from patients treated with antihypertensive and cardiac medications. The expression of protein p53, topoisomerase I (topo I), heat shock protein 90 (HSP90), and E-cadherin was analyzed using immunohistochemistry. RESULTS: The p53 protein expression showed a trend to a positive correlation with topo I expression in the total sample (p = 0.067, R = 0.25). The p53 protein and HSP90 expression was higher in the OLL group compared to the OLP group, but the difference was not statistically significant. No association was found between topo I and E-cadherin expression for either the OLP or OLL group. CONCLUSIONS: The findings of this study suggest that the slightly higher protein p53 and HSP90 expression in the OLL group might be caused by the medications used. The slight association between p53 and topo I expression indicates that the cooperation between these proteins might be essential for the growth of OLP/OLL in general. We conclude that the overexpression of p53 protein and high expression of topo I found in both types of lesions might induce their biologically aggressive behavior.

Identification of novel genome-wide pleiotropic associations with oral inflammatory traits.

Oral inflammatory diseases (OIDs) are a group of dental diseases with multiple clinical manifestations that impact the majority of the world's population. Many studies have investigated the associations between individual OID traits and genomic variants, but whether pleiotropic loci are shared by oral inflammatory traits remains poorly understood. Here, we conducted multitrait joint analyses based on the summary statistics of genome-wide association studies (GWASs) of five dental traits from the UK Biobank. Among these genome-wide significant loci, two were novel for both painful gums and toothache. We identified causal variants at each novel locus, and functional annotation based on multiomics data suggested IL10 and IL12A/TRIM59 as potential candidate genes at the novel pleiotropic loci. Subsequent analyses of pathway enrichment and protein-protein interaction networks suggested the involvement of the candidate genes in immune regulation. In conclusion, our results uncover novel pleiotropic loci for OID traits and highlight the importance of immune regulation in the pathogenesis of OIDs. These findings will enhance our understanding of the pathogenesis of OIDs and be beneficial for risk screening, prevention, and the development of novel drugs targeting the immune regulation of OIDs.

Multiple approaches to oral epithelial dysplasia degree analyses: a pilot study.

BACKGROUND: Oral epithelial dysplasia (OED) is the presence of cells of an abnormal type within a tissue, which may signify a stage preceding the development of cancer. Our aim was to determine the interrelation between the expression of multiple molecular markers and the histological features of oral dysplasia. METHODS: Fifteen samples of OED (five for each severity degree) were analyzed through software assisted image cytometry nuclear morphology. p53 (wild-type and mutated form), Bax and Bcl2 expression was immunohistochemically determined, and the gene expression of MMP1, MMP2, MMP9 and hTERT was determined by RT-PCR. The mean, standard deviation, ANOVA and Fisher's Exact Test (P<0.05) were performed. RESULTS: Our analysis indicated congruence between the software-assisted measurement of nuclear morphology and severity degree. Only five samples were positive to p53-mutated form; and Bax was more expressed than Bcl-2. hTERT expression was significantly expressed in relation to severity, and MMP1 was predominantly expressed, followed by MMP9 and MMP2. CONCLUSIONS: Our results reinforce that software-assisted measurement is an alternative to severity degree determination. MMP1 is an important marker for severity dysplasia degree; however, the predominant expression of Bax over Bcl-2 suggests that this pro-apoptotic state could be used to minorize the progression, perhaps, as a future therapeutic target.

"Oral Manifestations of Patients with Inherited Defect in Phagocyte Number or Function" a systematic review.

INTRODUCTION: Inherited phagocyte defects are one of the subgroups of primary immunodeficiency diseases (PIDs) with various clinical manifestations. As oral manifestations are common at the early ages, oral practitioners can have a special role in the early diagnosis. MATERIALS AND METHODS: A comprehensive search was conducted in this systematic review study and data of included studies were categorized into four subgroups of phagocyte defects, including congenital neutropenia, defects of motility, defects of respiratory burst, and other non-lymphoid defects. RESULTS: Among all phagocyte defects, 12 disorders had reported data for oral manifestations in published articles. A total of 987 cases were included in this study. Periodontitis is one of the most common oral manifestations. CONCLUSION: There is a need to organize better collaboration between medical doctors and dentists to diagnose and treat patients with phagocyte defects. Regular dental visits and professional oral health care are recommended from the time of the first primary teeth eruption in newborns.

Towards better understanding of giant cell granulomas of the oral cavity.

Giant cell granulomas are enigmatic lesions of the oral cavity characterised by a peculiar combined proliferation of mononuclear and multinucleated giant cells in a mesenchymal stromal background. Central and peripheral giant cell granulomas may have similar pathogenesis and histology but differ in their location and biological behaviour. It is important to differentiate them from other giant cell lesions that can occur in the oral cavity, such as giant cell tumour of the bone, aneurysmal bone cyst, brown tumour of hyperparathyroidism, and giant cell lesions of Ramon syndrome, Noonan syndrome, neurofibromatosis and Jaffe-Campanacci syndrome. A recent insight into their molecular genetics and pathogenesis, with identification of KRAS, FGFR1 and TRPV4 mutations, allows for better diagnostic differentiation and opens the door to the use of pathway inhibitors in the treatment of recurrent or dysmorphic lesions. In this review, we provide an updated summary of the clinical and pathological features of oral cavity giant cell granulomas that help with their precise diagnosis and management.

Primary Immunodeficiencies With Defects in Innate Immunity: Focus on Orofacial Manifestations.

The field of primary immunodeficiencies (PIDs) is rapidly evolving. Indeed, the number of described diseases is constantly increasing thanks to the rapid identification of novel genetic defects by next-generation sequencing. PIDs are now rather referred to as "inborn errors of immunity" due to the association between a wide range of immune dysregulation-related clinical features and the "prototypic" increased infection susceptibility. The phenotypic spectrum of PIDs is therefore very large and includes several orofacial features. However, the latter are often overshadowed by severe systemic manifestations and remain underdiagnosed. Patients with impaired innate immunity are predisposed to a variety of oral manifestations including oral infections (e.g., candidiasis, herpes gingivostomatitis), aphthous ulcers, and severe periodontal diseases. Although less frequently, they can also show orofacial developmental abnormalities. Oral lesions can even represent the main clinical manifestation of some PIDs or be inaugural, being therefore one of the first features indicating the existence of an underlying immune defect. The aim of this review is to describe the orofacial features associated with the different PIDs of innate immunity based on the new 2019 classification from the International Union of Immunological Societies (IUIS) expert committee. This review highlights the important role played by the dentist, in close collaboration with the multidisciplinary medical team, in the management and the diagnostic of these conditions.

An IL-17F.S65L Knock-In Mouse Reveals Similarities and Differences in IL-17F Function in Oral Candidiasis: A New Tool to Understand IL-17F.

Oropharyngeal candidiasis (OPC) is an opportunistic infection of the oral mucosa caused by the commensal fungus Candida albicans IL-17R signaling is essential to prevent OPC in mice and humans, but the individual roles of its ligands, IL-17A, IL-17F, and IL-17AF, are less clear. A homozygous IL-17F deficiency in mice does not cause OPC susceptibility, whereas mice lacking IL-17A are moderately susceptible. In humans, a rare heterozygous mutation in IL-17F (IL-17F.S65L) was identified that causes chronic mucocutaneous candidiasis, suggesting the existence of essential antifungal pathways mediated by IL-17F and/or IL-17AF. To investigate the role of IL-17F and IL-17AF in more detail, we exploited this "experiment of nature" by creating a mouse line bearing the homologous mutation in IL-17F (Ser65Leu) by CRISPR/Cas9. Unlike Il17f-/- mice that are resistant to OPC, Il17fS65L/S65L mice showed increased oral fungal burdens similar to Il17a -/- mice. In contrast to humans, however, disease was only evident in homozygous, not heterozygous, mutant mice. The mutation was linked to modestly impaired CXC chemokine expression and neutrophil recruitment to the infected tongue but not to alterations in oral antimicrobial peptide expression. These findings suggest mechanisms by which the enigmatic cytokine IL-17F contributes to host defense against fungi. Moreover, because these mice do not phenocopy Il17f-/- mice, they may provide a valuable tool to interrogate IL-17F and IL-17AF function in vivo in other settings.

Oral and nail pigmentations: a useful parallelism for the clinician.

Oral (OP) and nail (NP) pigmentations may occur simultaneously in physiological or pathological conditions, and may be a sign of underlying syndromic conditions that necessitate further investigation and treatment. Interestingly, the nail unit and oral cavity show a clinical parallelism that may help the clinician to conduct a correct examination and reach a prompt diagnosis. Both OP and NP can manifest clinically with focal or diffuse involvement and are due to external factors (exogenous pigmentation, drug-induced pigmentation) or endogenous factors (racial pigmentation, post-inflammatory pigmentation, nevi, genetic conditions and other disorders). The most concerning differential diagnosis is melanoma. Here we report the pathogenetic basis of OP and NP, together with the description of similar clinical features. To the best of our knowledge this is the first paper to summarize and describe the causes of pigmentation of both the oral cavity and the nail unit.

Marijuana-Derived Cannabinoids Trigger a CB2/PI3K Axis of Suppression of the Innate Response to Oral Pathogens.

Cannabis use is an emergent risk factor for periodontitis, a chronic bacterial-induced disease of the supporting structures of the teeth. However, the mechanisms by which marijuana exposure predisposes to periodontal tissue destruction have yet to be elucidated. Therefore, we examined the influence of physiologically relevant doses of major marijuana-derived phytocannabinoid subtypes (cannabidiol [CBD]; cannabinol [CBN]; and tetrahydrocannabinol [THC], 1.0 µg/ml) on the interactions of three ultrastructurally variant oral pathogens, Porphyromonas gingivalis, Filifactor alocis, and Treponema denticola with the immune system. CBD, CBN, and THC each suppressed P. gingivalis-induced IL-12 p40, IL-6, IL-8, and TNF release while enhancing the anti-inflammatory cytokine, IL-10, from human innate cells. Similar phenomena were observed in F. alocis- and T. denticola-exposed human monocytes and human gingival keratinocytes. Higher phytocannabinoid doses (≥5.0 µg/ml) compromised innate cell viability and inhibited the growth of P. gingivalis and F. alocis, relative to unexposed bacteria. T. denticola, however, was resistant to all cannabinoid doses tested (up to 10.0 µg/ml). Pharmaceutical inhibition and efficient gene silencing indicated that a common CB2/PI3K axis of immune suppression is triggered by phytocannabinoids in vitro. This pathway does not appear to perpetuate through the canonical GSK3ß-dependent cholinergic anti-inflammatory pathway, the predominant endogenous inflammatory control system. In a repetitive, transient oral infection model, CBD also suppressed P. gingivalis-induced innate immune markers in wild-type mice, but not in CB2-/- mice. If such phenomena occur in humans in situ, environmental cannabinoids may enhance periodontitis via direct toxic effects on specific oral bacteria; by compromising innate cell vitality; and/or through a suppressed innate response to periodontal pathogens involving a CB2/PI3K signaling lineage.

Therapeutic effects of bone mesenchymal stem cells on oral and maxillofacial defects: a novel signaling pathway involving miR-31/CXCR4/Akt axis.

Context: Although bone mesenchymal stem cells (BMSCs) have been used for the treatment of oral and maxillofacial defects, the survival rate and limited proliferation reduces the therapeutic efficiency of BMSC.Objective: The aim of our study is to explore the role of miR-31 in regulating survival, proliferation, and migration of BMSC in vitro.Materials and methods: LPS was used in vitro to induce BMSC damage and then miR-31 was used to incubate with BMSC. Subsequently, BMSC proliferation, survival, and migration were determined via ELISA, qPCR, western blots, and immunofluorescence.Results: The expression of miR-31 was downregulated in response to LPS stress. Interestingly, supplementation of miR-31 could reverse the survival, proliferation and migration of BMSC under LPS. Mechanically, miR-31 treatment inhibited the activation of caspase, and thus promoted BMSC survival. Besides, miR-31 upregulated the genes related to cell proliferation, an effect that was followed by an increase in the levels of migratory factors. Further, we found that miR-31 treatment activated the CXCR4/Akt pathway and blockade of CXCR4/Akt could abolish the beneficial effects of miR-31 on BMSC proliferation, survival, and migration.Conclusions: miR-31 could increase the therapeutic efficiency of BMSC via the CXCR4/Akt pathway.

Unpredictable Effects of the Genetic Background of Transgenic Lines in Physiological Quantitative Traits.

Physiology, fitness and disease phenotypes are complex traits exhibiting continuous variation in natural populations. To understand complex trait gene functions transgenic lines of undefined genetic background are often combined to assess quantitative phenotypes ignoring the impact of genetic polymorphisms. Here, we used inbred wild-type strains of the Drosophila Genetics Reference Panel to assess the phenotypic variation of six physiological and fitness traits, namely, female fecundity, survival and intestinal mitosis upon oral infection, defecation rate and fecal pH upon oral infection, and terminal tracheal cell branching in hypoxia. We found continuous variation in the approximately 150 strains tested for each trait, with extreme values differing by more than four standard deviations for all traits. In addition, we assessed the effects of commonly used Drosophila UAS-RNAi transgenic strains and their backcrossed isogenized counterparts, in the same traits plus baseline intestinal mitosis and tracheal branching in normoxia, in heterozygous conditions, when only half of the genetic background was different among strains. We tested 20 non-isogenic strains (10 KK and 10 GD) from the Vienna Drosophila Resource Center and their isogenized counterparts without Gal4 induction. Survival upon infection and female fecundity exhibited differences in 50% and 40% of the tested isogenic vs. non-isogenic pairs, respectively, whereas all other traits were affected in only 10-25% of the cases. When 11 isogenic and their corresponding non-isogenic UAS-RNAi lines were expressed ubiquitously with Gal4, 4 isogenic vs. non-isogenic pairs exhibited differences in survival to infection. Furthermore, when a single UAS-RNAi line was crossed with the same Gal4 transgene inserted in different genetic backgrounds, the quantitative variations observed were unpredictable on the basis of pure line performance. Thus, irrespective of the trait of interest, the genetic background of commonly used transgenic strains needs to be considered carefully during experimentation.

A New Approach for the Diagnosis of Systemic and Oral Diseases Based on Salivary Biomolecules.

Early diagnosis represents the target of contemporary medicine and has an important role in the prognosis and further treatment. Saliva is a biofluid that generated a high interest among researchers due to its multiple advantages over other body fluids. The multitude of components that can act as biomarkers influenced the existing technologies to develop protocols that could allow saliva to become the new noninvasive diagnostic method. Saliva as a diagnostic tool can bring substantial addition to the diagnostic armamentarium, providing important information about oral and general health. The diagnostic applications of saliva extended and had a rapid evolution due to the advancement in salivaomics. The present review summarizes the latest researches in saliva-related studies and explores the information and correlations that saliva can offer regarding the systemic and oral diseases, highlighting its great potential of diagnosis. It is expected that in the future specific guidelines and results regarding the salivary diagnostics are to be available, together with high-sensitivity and specificity tests for multiple systemic and oral diseases.

SATB2-associated syndrome (SAS) and associated dental findings.

OBJECTIVE: Identify, diagnose, and document oral clinical and radiographic evidence associated with the genetic condition known as special AT-rich sequence-binding protein 2 (SATB2)-associated syndrome. Through identifying and publishing these common dental and behavioral findings, we hope to educate oral and medical healthcare providers to identify this condition in an attempt to develop meaningful comprehensive care to this patient population. METHODS: A total of 37 patients (19 female), ranging from ages 2 to 20 were evaluated at Arkansas Children's Hospital in Little Rock, Arkansas. Patient geographic distribution included: the United States, Canada, Portugal, Spain, and the Netherlands. Patients were clinically and radiographically examined for oral findings. Panoramic radiographs were obtained when patient's behavior allowed. Patient's parents or guardians were also interviewed concerning dental, medical, and behavioral histories. RESULTS: Clinical findings included delayed tooth eruption, bruxism, sialorrhea, larger than normal teeth with an increased propensity for maxillary anterior tooth trauma due to unsteady ambulation. Radiographic findings included delayed permanent root formation, significantly delayed or missing second bicuspids, malformed teeth, and taurodontism. Medical and behavioral issues included: insomnia, hyperphagia, cognitive delays, and an extremely high pain threshold. CONCLUSION: Patients with SATB2-associated syndrome have shown to have a consistent and unique set of dental findings both clinically and radiographically. A thorough health and dental history along with the aforementioned results of the study may facilitate a diagnosis of this syndrome. Due to the complexity of the patient's dental needs and behavior, a health practitioner with special needs care experience on a comprehensive craniofacial team would be optimal.

Diseases of the oral cavity in light of the newest epigenetic research: Possible implications for stomatology.

Epigenetics is the study of inheritable changes in gene expression without changes in the underlying deoxyribonucleic acid (DNA) sequence. The main mechanisms of epigenetic regulation include DNA methylation, modifications in histones, and micro-ribonucleic acids (miRNA). Recent research evidence has shown that environmental and lifestyle factors dynamically interact with the genome, influencing epigenetic changes, from development to the later stages of life. This happens across a spectrum, from physiological to pathological conditions, such as genetic defects, developmental disorders, infectious or inflammatory processes, cancers, mental disorders, and substance abuse. Epigenetic studies have been conducted in various medical disciplines (e.g., oncology, internal medicine or psychiatry), adding valuable insight to standard medical approaches. However, in stomatology, epigenetic research is still in its infancy; thus, this review is aimed at presenting the role of epigenetic mechanisms in diseases of the oral cavity, including periodontal diseases, caries, developmental anomalies, and oral carcinoma. In addition, this paper reveals new insights into epigenetic biomarkers that can be helpful in the detection, early diagnosis, prognosis, and treatment of different oral diseases. Moreover, this review is focused on the possible clinical implications (diagnostic and therapeutic) of epigenetics, in the form of some noninvasive methods that can possibly be used in the future for the screening, work-up, outcome prediction and novel treatments of some dental diseases. Finally, this paper highlights that an epigenetic approach can be useful for designing novel interventions that will improve the management of oral malignancies or developmental abnormalities.

DC-SIGN and VDR polymorphisms are associated with chronic form of paracoccidioidomycosis with oral manifestations.

Paracoccidioidomycosis (PCM) is a granulomatous disease caused by fungi of the species complex of the Paracoccidioides genus. One of the main clinical manifestations of PCM is the presence of oral lesions with the presence of epithelioid granulomas. In this work, we aimed to evaluate the frequency of SNPs in the TNF-α, JAK1, VDR, DC-SIGN and FcγRIIa genes in patients with chronic PCM and verify possible association of these SNPs with the organisation pattern of the granulomas in the oral lesions. A total of 66 samples of DNA were obtained from oral lesions biopsies and 106 DNA samples were obtained from healthy individuals. The individuals were genotyped for SNPs in DC-SIGN (rs4804803), FcγRIIa (rs1801274), JAK1 (rs11208534), TNF-α (rs1800629) and VDR (rs7975232) by real-time PCR and allele discrimination method. Granulomas were classified as loose or dense according to the histological pattern. In the VDR (rs7975232), the CC genotype (P < 0.001, OR = 5.94, 95% CI = 2.07-17.05), and the C allele (P = 0.027, OR = 2.71, 95% CI = 1.07-6.86), as well as the GG genotype in DC-SIGN (rs4804803) (P = 0.032, OR: 3.76, 95%, I = 1.06-13.38) are associated with an increased risk of oral PCM. Our data indicate that VDR and DC-SIGN genetics variations are related to the susceptibility of oral PCM in the group of patients analysed.

Herpesviruses and MicroRNAs: New Pathogenesis Factors in Oral Infection and Disease?

The oral cavity incessantly encounters a plethora of microorganisms. Effective and efficient oral innate and adaptive immune responses are incumbent to maintain healthy mucosa. A higher prevalence of Human Herpesviruses (HHV), a family of large enveloped DNA viruses, has been reported in multiple oral inflammatory diseases suggesting their involvement in disease progression. However, the viral components contributing to oral disease remain obscure. MicroRNAs (miRNA) are non-protein coding, single stranded ribonucleic acid (RNA) molecules that post-transcriptionally regulate diverse messenger RNAs. Thus, miRNAs can control large repertoire of biological processes. Changes in miRNA expression are associated with various oral infections and diseases. Cellular miRNAs can act as pro- or anti-viral factors and dysregulation of host miRNA expression occurs during herpesviruses infection. This strongly suggest a critical role of cellular miRNAs in host-herpesvirus interaction. Interestingly, HHV also encode multiple miRNAs (called viral miRNAs) that may play key role in host-pathogen interaction by modulating both host biological pathways and controlling viral life cycle. Recent studies from our laboratory have identified viral miRNAs (v-miRs) in diseased oral tissue biopsies and demonstrate their immunomodulatory roles. This review discusses the association of miRNAs (both host and viral) and herpesviruses in the pathogenesis of oral inflammatory diseases.

Genetic Variations of OPRM1, OPRK1, and COMT Genes and Their Possible Associations with Oral Pain in a Population from Argentina.

AIMS: To analyze in a population from Argentina the variation of three genes involved in the control of pain pathways-two genes that code for opioid receptors (OPRM1 and OPRK1) and COMT, which codes for an important enzyme in the control of neurotransmission-and to evaluate the associations of these genes with oral pain and the need for analgesics in the population under study. METHODS: A total of 134 volunteer donors from the city of Resistencia and 27 donors from the Wichí community for comparison were analyzed for 13 single nucelotide polymorphisms (SNPs) and 1 insertion/deletion (Indel) localized in the three genes using polymerase chain reaction-restriction fragment length polymorphism or standard PCR and electrophoresis. All 134 individuals from Resistencia provided biologic samples for DNA analysis, and a subset (n = 81) agreed to answer a questionnaire for an association analysis. Statistical tests for a possible association between genetic variation and self-reported ethnic origin, oral pain, and need for analgesic drugs were performed. RESULTS: Significant differences were found when the study population was compared to populations from other continents, as well as between the two studied populations (P < .05). A positive association was suggested for the COMT gene from Resistencia with both oral pain intensity and analgesic requirements. CONCLUSION: The admixture process that occurred in the past of Resistencia probably contributed to a genetic differentiation in this population, and this genetic variation might influence phenotypic expressions of pain perception and analgesic requirements.