Cleber Machado de Souza

Association between Vitamin D Receptor Gene Polymorphisms and Susceptibility to Chronic Kidney Disease and Periodontitis

Background/Aims: Chronic kidney disease (CKD) and periodontitis (PD) are serious public-health concerns. Vitamin D is a fat-soluble steroid hormone that interacts with its nuclear receptor (VDR) to regulate a variety of biological processes, such as bone metabolism, immune response modulation and transcription of several genes involved in CKD and PD disease mechanisms. The aim of this work was to investigate the association between polymorphisms in the VDR gene and end-stage renal disease (ESRD) and PD. Methods: 222 subjects with and without ESRD (in hemodialysis) were divided into groups with and without PD. Polymorphisms TaqI and BsmI in the VDR gene were analyzed by PCR restriction fragment length polymorphism. The significance of differences in allele, genotype and haplotype frequencies between groups was assessed by the χ2 test (p value <0.05) and odds ratio (OR). Results: Allele G was associated with protection against ESRD: groups without versus with ESRD (GG) × (GA+AA): OR = 2.5, 95% CI = 1.4–4.6, p = 0.00; (G × A): OR = 1.5, 95% CI = 1.0–2.3, p = 0.02; (TG + CG) × (TA + CA): OR = 1.5, 95% CI = 1.0–2.3, p = 0.02. No association was observed between the study polymorphisms and susceptibility to or protection against PD. Conclusion: Allele G of the VDR BsmI polymorphism was associated with protection against ESRD.

ORAL HEALTH IN BRAZILIAN PATIENTS WITH CHRONIC RENAL DISEASE

BACKGROUND Poor oral health status may have an impact on the health status of patients with chronic renal failure. AIM To describe the oral health status of a group of Brazilian patients with chronic renal failure. MATERIAL AND METHODS Retrospective review of the medical records of patients with chronic renal failure, of whom 13 (4.5%) were in a predialysis stage, 158 (55%) were on hemodialysis, 23 (8.4%) were on peritoneal dialysis and 92 (32.1%) were transplanted. General oral health, presence of dental calculus, and halitosis were recorded. The number of decayed, missed and filled teeth was analyzed by means of DMF-T (Decayed, Missed and Filled Teeth) index. RESULTS The sample was composed of 152 men (53%) and 134 women (47%), aged 42+/-13 years. Oral health status was considered defective in most patients (83%). Eighty-seven percent had dental calculus and 55% had halitosis. Transplant patients reported significantly less halitosis (40.2%) than the rest of the groups. The DMF-T for the whole population was 20.6 and had a positive correlation with age. CONCLUSIONS This group of patients with chronic renal failure presented a poor oral health status. Dental treatment programs for these patients should be implemented to avoid the exposure to dental pathogens.

Association Among Oral Health Parameters, Periodontitis, and Its Treatment and Mortality in Patients Undergoing Hemodialysis

BACKGROUND Chronic periodontitis (CP) is a continuous, reversible source of inflammation with a potential impact on mortality in patients undergoing hemodialysis (HD). This study investigates the impact of oral health indicators, CP, and its treatment on survival rates in a group of patients undergoing HD. METHODS Clinically stable patients undergoing HD were referred for a dental examination. All patients were prospectively followed in the dialysis clinic, and all-cause mortality was recorded. Three groups of patients were analyzed: those who received CP treatment, those who did not, and patients without CP as a control group. RESULTS A total of 122 patients (79 males and 43 females, aged 23 to 77 years; mean age: 50 years; range: 23 to 77 years) were enrolled. Forty percent reported having rarely been evaluated by a dentist, and 59% had CP. There were 34 fatal events during a mean follow-up time of 64.1 ± 11.2 months. Oral factors associated with death in the univariate analysis were decreased frequency of dental visits; non-use of dental floss; increased decayed, missing, and filled teeth index; presence of CP; and absence of CP treatment. Patients with CP had a higher risk of death from all causes compared with patients without CP in the univariate analysis for untreated patients (hazard ratio 2.65 [95% confidence interval 1.06 to 6.59]; P = 0.036) and to a lesser extent for treated patients (2.36 [1.01 to 5.59]; P = 0.047). These significant differences were not maintained after adjustments for confounders in the multivariate model. CONCLUSIONS These results suggest that poor oral health, including CP, is a common finding in patients undergoing HD. The results of this study call for intervention trials to test the hypothesis that treatment of CP improves survival in maintenance of patients undergoing HD.

Analysis of IL1 gene polymorphisms and transcript levels in periodontal and chronic kidney disease.

UNLABELLED Chronic kidney disease (CKD) and periodontitis (PD) are complex inflammatory disturbances, influenced by genetic factors. Interleukin (IL)-1 genes code for inflammatory mediators involved in the physiopathogenesis of both diseases. Functional polymorphisms in IL1 genes modulate cytokine levels and have been associated with susceptibility to immune-inflammatory conditions. OBJECTIVES The aim of this study was investigate the association of functional IL1 gene polymorphisms and transcript levels with susceptibility to CKD and PD. DESIGN The sample consisted of 246 individuals, mean age 44.8 years, divided into: group 1 (64 patients without CKD and without PD), group 2 (58 without CKD and with PD), group 3 (52 with CKD and without PD) and group 4 (72 with CKD and with PD). DNA was obtained from cells of oral mucosa and polymorphisms IL1AC-889T, IL1BC-511T, IL1BC+3954T and IL1RN (intron 2) were analyzed by PCR-RFLP. Transcript levels from gingival tissues were analyzed by real-time PCR. RESULTS IL1RN(*)1 allele was associated with almost 4-fold increased risk for CKD (OR 3.92 95% CI=1.6-9.4, p=0.002). IL1RN(*)2 allele was associated with 3-fold increased risk for PD in CKD patients (OR 3.08 95% CI=1.2-7.9, p=0.019). Allele T for polymorphism IL1B+3954 was associated with CKD in PD patients (OR 2.28 95% CI=1.1-4.7, p=0.019). Significantly increased levels of transcripts of IL1A, IL1B and IL1RN genes were found in PD patients. CONCLUSIONS It was observed an evidence for association of IL1B and IL1RN alleles with susceptibility to CKD and PD. Higher levels of IL1 gene transcripts were found in PD patients.

Association analysis of clinical aspects and vitamin D receptor gene polymorphism with external apical root resorption in orthodontic patients

INTRODUCTION Vitamin D is responsible for the regulation of certain genes at the transcription level, via interaction with the vitamin D receptor, and influences host immune responses and aspects of bone development, growth, and homeostasis. Our aim was to investigate the association of TaqI vitamin D receptor gene polymorphism with external apical root resorption during orthodontic treatment. METHODS Our subjects were 377 patients with Class II Division 1 malocclusion, divided into 3 groups: (1) 160 with external apical root resorption ≤1.43 mm, (2) 179 with external apical root resorption >1.43 mm), and (3) 38 untreated subjects. External apical root resorption of the maxillary incisors was evaluated on periapical radiographs taken before and after 6 months of treatment. After DNA collection and purification, vitamin D receptor TaqI polymorphism analysis was performed by polymerase chain reaction-restriction fragment length polymorphism. Univariate and multivariate analyses were performed to verify the association of clinical and genetic variables with external apical root resorption (P <0.05). RESULTS There was a higher proportion of external apical root resorption in orthodontically treated patients compared with the untreated subjects. In patients orthodontically treated, age higher than 14 years old, initial size of the maxillary incisor root superior to 30 mm, and premolar extraction were associated with increased external apical root resorption. Genotypes containing the C allele were weakly associated with protection against external apical root resorption (CC + CT × TT [odds ratio, 0.29; 95% confidence interval, 0.07-1.23; P = 0.091]) when treated orthodontic patients were compared to untreated individuals. CONCLUSIONS Clinical factors and vitamin D receptor TaqI polymorphism were associated with external apical root resorption in orthodontic patients.

Analysis of the association of an MMP1 promoter polymorphism and transcript levels with chronic periodontitis and end-stage renal disease in a Brazilian population

UNLABELLED Chronic periodontitis (CP) and end-stage renal disease (ESRD) are complex inflammatory conditions. Higher levels of MMP-1 were found in fluids and gingival tissues from CP patients and in the blood and tissues from ESRD patients. MMP1-1607 (1G/2G) is a functional polymorphism, as it alters MMP-1 expression. OBJECTIVE The aim of this study was to investigate the association of the MMP1-1607 (1G/2G) polymorphism with CP and ESRD and evaluate differences in transcript levels between the groups. DESIGN A total of 254 individuals were divided into four groups: Group 1, without CP and without chronic kidney disease (CKD) (n = 67); Group 2, with CP and without CKD (n = 60); Group 3, without CP and with CKD stage 5 (ESRD) (n = 52), and Group 4, with CP and with ESRD (n = 75). The MMP1-1607 polymorphism was analysed by PCR-RFLP. MMP1 gene transcripts from gingival tissues were analysed by real-time PCR. RESULTS No association was found between the MMP1-1607 polymorphism and CP or ESRD. Increased levels of MMP1 transcripts were observed in CP patients with or without ESRD. No differences were observed in the transcript levels according to the genotypes. CONCLUSION It was concluded that the MMP1-1607 polymorphism was not associated with either CP or ESRD. However, higher levels of MMP1 gene transcripts were found at gingival sites of CP in patients both with and without ESRD.

Comparative Analysis of Psychological, Hormonal, and Genetic Factors Between Burning Mouth Syndrome and Secondary Oral Burning

OBJECTIVE The objective of this study was to evaluate the association between psychological, hormonal, and genetic factors with the development of burning mouth syndrome (BMS) and secondary oral burning (SOB) in order to provide a better characterization and classification of these conditions. DESIGN Cross sectional study. SETTING Patients with complaints of mouth burning registered at the Oral Diagnostic Service of the Federal University of Rio Grande do Norte between 2000 and 2013. SUBJECTS The sample consisted of 163 subjects divided into a group of patients with BMS (n = 64) and a group of subjects with SOB (n = 99). METHODS The following variables were analyzed: passive and stimulated saliva flow, stress levels and phase, depression, anxiety, serum cortisol and dehydroepiandrosterone (DHEA) levels, and the presence of polymorphisms in the interleukin 6 (IL-6) gene. RESULTS The results showed significant differences in the presence of xerostomia (p = 0.01), hyposalivation at rest (p < 0.001) and symptoms of depression (p = 0.033) between the two groups, which were more prevalent in the BMS group. DHEA levels were lower in the BMS group (p = 0.003) and were sensitive and specific for the diagnosis of this condition. Genetic analysis revealed no significant association between the polymorphisms analyzed and the development of BMS. CONCLUSION These results suggest a possible role of depression, as well as of reduced DHEA levels, as associated factors for development of BMS.

Host and clinical aspects in patients with benign migratory glossitis

OBJECTIVE Investigate the association of clinical, cytological and genetic characteristics with benign migratory glossitis (BMG). STUDY DESIGN Sample consisted of 175 patients, 44 with BMG and 131 control patients. Clinical examination and DMFT index were assessed. Cytological evaluation determined cell morphology and morphometry. Genetic evaluation was performed by analysing IL6 polymorphisms by real-time PCR. Univariate and multivariate analyses were performed (p<0.05). RESULTS There was a higher level of anxiety, DMFT score and a prevalence of fissured tongue in BMG group. A high mean nuclear/cytoplasmic area ratio was observed in patients with BMG. There was predominance of Papanicolaou class II I BMG group. IL6 allele G rs2069843 polymorphism was associated with BMG in the dominant model. In multivariate analysis, DMFT and anxiety scale remained associated with BMG.

Association of a PARK2 Germline Variant and Epithelial Ovarian Cancer in a Southern Brazilian Population

Ovarian cancer (OC) is the eighth most common cancer among women in Brazil and seventh in the world population. OC has a high mortality rate and is difficult to diagnose. Currently, OC detection most often occurs at an advanced stage of the disease due to its silent progression, which contributes to the high mortality rate. Available genetic markers are not considered specifically enough for an initial and definite diagnosis. The association with new genes involved with OC can provide a better understanding of this pathology as well as contribute to the development of a marker scenario, providing an improvement in the treatment and survival of patients. The aim of this study was to examine the potential association between the PARK2 gene and epithelial ovarian cancer (EOC). Accordingly, we conducted a study for which 25 patients and 87 controls were recruited. Linkage disequilibrium analysis showed that the four studied tag SNPs (rs2803073, rs6930532, rs1040079, and rs2276201) were independent. Our results using the multivariate analysis between the additive and dominant model demonstrated that tag SNP rs2803073 of PARK2 is associated with susceptibility to EOC (p = 0.018, OR = 0.42). These findings suggest that hereditary variation in the PARK2 gene could influence EOC development mechanisms.

Clinical aspects and polymorphisms in the LTA, TNFA, LTB genes and association with dental implant loss

BACKGROUND This study shows the relationship between host factors and environmental factors in the influence of susceptibility to loss of dental implants. PURPOSE The aim of this study was to investigate the association of clinical aspects and tag SNPs of the genes LTA, TNFA, and LTB with dental implant loss. MATERIALS AND METHODS The subjects consisted of 244 patients, divided into two groups: control group (C)-163 individuals who did not lose any implants, being in function for at least 6 months; and study group (S)-81 individuals who had lost at least one implant. DNA was collected from saliva, and the genotypes were determined by real time PCR. Univariate and multivariate analysis were employed p < .05. RESULTS After multivariate analysis, dental implant loss remained associated with the presence of teeth (p = .011), a larger amount of placed implants (p = .001), and allelle C of rs2009658 of the LTA gene (p = .006). For the other tag SNPs of these studied genes, there was no association between the groups C and S with dental implants loss. CONCLUSION Presence of teeth, number of placed implants and allele C of rs2009658 of LTA gene were associated with implant loss.