UCP2 polymorphisms, daily step count, and number of teeth associated with all-cause mortality risk in Sado City: A hospital-based cohort study.

Objective: Uncoupling protein 2 (UCP2) is an ion/anion transporter in the mitochondrial inner membrane that plays a crucial role in immune response, regulation of oxidative stress, and cellular metabolism. UCP2 polymorphisms are linked to chronic inflammation, obesity, diabetes, heart disease, exercise efficiency, and longevity. Daily step count and number of teeth are modifiable factors that reduce mortality risk, although the role of UCP2 in this mechanism is unknown. This study aimed to assess the possible effects of UCP2 polymorphisms on the association between daily step count and number of teeth with all-cause mortality. Methods: This study was conducted as a cohort project involving adult Japanese outpatients at Sado General Hospital (PROST). The final number of participants was 875 (mean age: 69 y). All-cause mortality during thirteen years (from June 2008 to August 2021) was recorded. The functional UCP2 genotypes rs659366 and rs660339 were identified using the Japonica Array®. Survival analyses were performed using multivariate Cox proportional hazard models. Results: There were 161 deaths (mean observation period: 113 months). Age, sex, daily step count, and the number of teeth were significantly associated with mortality. In females, UCP2 polymorphisms were associated with mortality independent of other factors (rs659366 GA compared to GG + AA; HR = 2.033, p = 0.019, rs660339 C T compared to CC + TT; HR = 1.911, p = 0.029). Multivariate models, with and without UCP2 genotypes, yielded similar results. The interaction terms between UCP2 genotype and daily step count or number of teeth were not significantly associated with mortality. Conclusion: The effects of UCP2 polymorphisms on the association between daily step count or the number of teeth and all-cause mortality were not statistically significant. In females, UCP2 polymorphisms were significantly associated with all-cause mortality. Our findings confirmed the importance of physical activity and oral health and suggested a role of UCP2 in mortality risk independently with those factors.

Association among periodontitis severity, anti-agalactosyl immunoglobulin G titer, and the disease activity of rheumatoid arthritis.

OBJECTIVE: The aim of the present study was to evaluate the association between the periodontal and serological parameters and the disease activity of rheumatoid arthritis (RA) and between the anti-agalactosyl immunoglobulin G (IgG) titer and periodontitis severity. The objective was also to assess the effect of supragingival scaling on the serological parameters in patients with RA. BACKGROUND: The periodontal and serological parameters in relation to the autoimmune inflammatory response have been linked to RA disease activity. However, the association of the anti-agalactosyl IgG titer with RA disease activity and periodontitis severity has not been elucidated. METHODS: The periodontal, rheumatologic, and serological data were collected from 127 patients with RA in a retrospective cohort study. Of the 127 patients, 21 had been randomly assigned to receive oral hygiene instruction and supragingival scaling. The anti-agalactosyl IgG titer was determined by an electrochemiluminescence immunoassay. RESULTS: The patients with a moderate to high RA disease activity showed significantly higher levels of probing depth (PD), clinical attachment level, anti-cyclic citrullinated peptide IgG, and anti-agalactosyl IgG titer and greater mean percentages of severe periodontitis than those with a low RA disease activity (p < .05 for all). Both univariate and multivariate analyses revealed a significantly positive correlation between the PD and RA disease activity (p = .009 and p = .001), between the anti-agalactosyl IgG titer and RA disease activity (p = .002 and p < .001), and between the anti-agalactosyl IgG titer and PD (p < .001 for both). Supragingival scaling significantly decreased the anti-agalactosyl IgG titer (p = 0.03). CONCLUSION: The PD and anti-agalactosyl IgG titer are positively interrelated, both of which are correlated positively with RA disease activity and influenced by supragingival scaling in patients with RA.

Association between serum IgG antibody titers against Porphyromonas gingivalis and liver enzyme levels: A cross-sectional study in Sado Island.

BACKGROUND: Previous studies have reported associations between nonalcoholic fatty liver disease, periodontitis, and obesity. Serum immunoglobulin G (IgG) antibody titer against Porphyromonas gingivalis, a major pathogen of periodontitis, is an established indicator of periodontal infection. However, the relationship between the antibody titer and liver enzyme levels has not been clarified yet. A study in the elderly was needed to evaluate the effect of long-term persistent bacterial infection on liver function. The objective of this study was to investigate the association between liver function and infection by P. gingivalis, and the effect of obesity on the association. METHODS: A cross-sectional study was conducted in adult outpatients visiting Sado General Hospital, in Niigata Prefecture, Japan, from 2008 to 2010. The final participants included 192 men and 196 women (mean age 68.1 years). Multivariable logistic regression analyses were performed to assess the association between the serum IgG antibody titer and the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and γ-glutamine transferase (GGT) levels. RESULTS: In women, serum IgG antibody titers against P. gingivalis was associated with elevated ALT, but not with AST or GGT, independent of covariates (p = 0.015). No significant association was found between the antibody titer and the elevated liver enzymes in men. The effect of obesity on the relationship between antibody titer and liver enzyme levels was not statistically significant. CONCLUSIONS: A cross-sectional analysis of adult outpatients suggested an association between P. gingivalis infection and ALT levels in women. The effect of obesity on this association was not statistically significant.

Impact of Local Drug Delivery of Minocycline on the Subgingival Microbiota during Supportive Periodontal Therapy: A Randomized Controlled Pilot Study.

The aim of this study was to examine the effect of adjunct local minocycline administration on the microbiological parameters of subgingival plaque samples in the residual periodontal pockets. Ten chronic periodontitis patients under a supportive periodontal therapy regimen were recruited. After subgingival debridement, either 2% minocycline gel, Periocline™, (Test Group) or a placebo (Control Group) was administered to the selected sites once a week for three weeks. Subgingival plaque was collected at baseline, and at four weeks and eight weeks. The microbiological composition was analyzed by 16S ribosomal RNA sequencing. In the Test Group, α-diversity (evenness) decreased compared to the baseline (p = 0.005) and was lower compared to the control group at four weeks (p = 0.003). The microbial community composition between the two groups was significantly different at four weeks (p = 0.029). These changes were attributable to a decrease in the bacteria associated with periodontitis and an increase in the bacteria associated with periodontal health. Additionally, the improvement in bleeding on probing continued at eight weeks; however, there were little microbial effects of 2% minocycline gel observed at eight weeks. The control group demonstrated no change throughout the eight-week experimental period. Thus, local minocycline administration can change the subgingival microbial community of residual periodontal pockets.

ß 2-Microglobulin and Neutrophil Gelatinase-Associated Lipocalin, Potential Novel Urine Biomarkers in Periodontitis: A Cross-Sectional Study in Japanese.

OBJECTIVES: Several serum biomarkers have been reported to increase in periodontitis patients as possible mediators linking periodontal inflammation to systemic diseases. However, the relationship between periodontitis and urine biomarkers is still unclear. The aim of this cross-sectional study was to investigate potential urine biomarkers of periodontitis in a Japanese population. MATERIALS AND METHODS: This study included 108 male subjects, and microbiological and clinical parameters were evaluated as a periodontitis marker. The correlation between nine urine biomarkers (typically used to diagnose kidney disease) and periodontal parameters was analyzed. Based on the findings, ß 2-microglobulin (ß 2-MG) and neutrophil gelatinase-associated lipocalin (NGAL) were selected for comparison and multivariate regression analysis, and the Kruskal-Wallis test followed by Bonferroni correction was used to identify differences in their concentrations between the three periodontitis groups (severe, moderate, and no/mild periodontitis). RESULTS: ß 2-MG and NGAL exhibited a significant correlation with clinical parameters of periodontitis. The prevalence of clinical parameters such as bleeding on probing and number of sites with probing depth (PD) ≥ 6 mm were greater in the ß 2-MG high group (≥300 µg/g creatinine) than in the normal group (P=0.017 and 0.019, respectively). Multivariate regression analysis indicated that the number of sites with PD ≥ 6 mm was independently associated with urine ß 2-MG. Moreover, the number of sites with the clinical attachment level (CAL) ≥ 6 mm was greater in the NGAL high group (highest quartile) (P=0.041). Multivariate regression analysis showed that the number of sites with CAL ≥ 6 mm was associated independently with urine NGAL. Finally, ß 2-MG was significantly higher in the severe periodontitis subjects compared to the no/mild periodontitis subjects. CONCLUSION: The significant association between urine ß 2-MG or NGAL and periodontitis was revealed. These biomarkers can potentially be used to screen for or diagnose periodontitis. This trial is registered with the UMIN Clinical Trials Registry UMIN000013485.

MAEA rs6815464 polymorphism and periodontitis in postmenopausal Japanese females: A cross-sectional study.

OBJECTIVES: Macrophage erythroblast attacher (MAEA) is a membrane protein that regulates the development of mature macrophages by mediating attachment with erythroblasts. A polymorphism rs6815464 (C/G) in MAEA gene was reported to be associated with type II diabetes. Along with diabetes, osteoporosis shows an increased prevalence in postmenopausal females, and both diseases have been reported to be associated with periodontitis. Therefore, we explored the relevance of the MAEA polymorphism to periodontitis, bone mineral density (BMD) and haemoglobin A1c (HbA1c). DESIGN: This was a cross-sectional study with the final sample comprised of 344 postmenopausal Japanese females. Probing pocket depth (PPD) and clinical attachment level (CAL) were measured. Genotype was determined by TaqMan assay. Blood biochemical parameters and BMD of the lumbar spine were evaluated. RESULTS: No differences were found in age, body mass index, HbA1c, BMD, number of teeth, bone metabolism parameters between the genotypes. Mean CAL and percentage of sites with PPD or CAL ≥ 5 mm were higher in the G-allele carriers than in the non-carriers. Multiple logistic regression analyses revealed that G-allele carriage was associated with severe periodontitis (odds ratio = 3.73, 95% CI = 1.36-10.19). CONCLUSION: Our results suggested that the MAEA gene polymorphism was independently associated with severe periodontitis.

A polymorphism rs6815464 in the macrophage erythroblast attacher gene is associated with low bone mineral density in postmenopausal Japanese women.

BACKGROUND AND PURPOSES: Osteoporosis and osteopenia are multifactorial diseases characterized by low bone mineral density (BMD) and are susceptible to genetic and environmental risk factors. The macrophage erythroblast attacher (MAEA) was discovered as a protein to mediate the attachment of erythroid cells to macrophages and is essential for bone marrow hematopoiesis. MAEA is expressed in a wide range of cells and tissues including osteoblasts and osteoclasts. Recent studies have shown that a single nucleotide polymorphism (SNP) rs6815464 (C/G) in the MAEA gene increases the susceptibility of type 2 diabetes mellitus. However, the contribution of MAEA to bone metabolism remains unknown. Therefore, we performed this study to evaluate the association between MAEA polymorphism and low BMD. METHODS: In a cross-sectional study with postmenopausal Japanese women living in the Yokogoshi area, Niigata City, we evaluated whether rs6815464 was associated with low BMD. Blood samples were collected from 353 subjects (age 63.8 ±â€¯5.4 years). The MAEA genotype was determined by TaqMan assay. BMD was assessed by dual-energy X-ray absorptiometry at the lumbar spine (L2-L4), hip and femoral neck. Low BMD was defined as a T-score <-1. RESULTS: The percentage of subjects with low BMD in the lumbar spine, total hip and femoral neck were 71%, 75% and 84% respectively. After adjusting age, BMI, HbA1c, smoking and alcohol consumption, the G-allele carriage was found to be associated with low BMD of total hip (odds ratio = 2.11, 95% CI: 1.14-3.91, P = 0.018), but not of the lumbar spine or femoral neck. CONCLUSION: The MAEA gene polymorphism rs6815464 was associated with low hip BMD in postmenopausal Japanese women.

Association of liver enzyme levels and alveolar bone loss: A cross-sectional clinical study in Sado Island.

BACKGROUND: The interaction of periodontopathic bacteria with host immune system induces the production of inflammatory mediators which leads to alveolar bone loss (ABL), the essential feature of periodontitis. Concurrently, periodontal diseases cause the elevation of blood cytokine levels, the alteration of gut microbiota and the dissemination of enterobacteria to the liver. Owing to these mechanisms, periodontal disease might be a risk for liver dysfunction. Several epidemiological studies have reported associations between periodontal diseases and liver dysfunction, although the association between ABL and liver dysfunction has not been investigated. This cross-sectional study determined if elevated serum liver enzyme levels were associated with ABL in Japanese adults. MATERIAL AND METHODS: Japanese adults living on Sado Island who visited Sado General Hospital were invited to participate in the study. Participants over 40 years of age who underwent dental panoramic radiography and blood tests were included. Drinking and smoking habits were self-administered. After excluding patients with edentulous jaw, diagnosed liver diseases, and those on dialysis, data from 44 men and 66 women with a mean age of 73 years were analyzed. The average percentage of ABL for each participant was calculated for mesial and distal sites of all remaining teeth. The levels of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) were determined. Univariate analyses were performed to select covariates to be put in multivariate analyses. The association between elevated serum liver enzyme levels and the highest quartile of ABL were assessed by multiple logistic regression analysis. RESULTS: After adjusting for covariates, no significant association was found between elevated serum AST, ALT, or GGT levels as dependent variables and the highest quartile of ABL as an explanatory variable. CONCLUSIONS: There was no significant association between the elevation of serum liver enzyme levels and ABL in Japanese adults. Key words:Liver enzymes, dental panoramic radiography, alveolar bone loss, Japanese adults.

Circulating levels of carbamylated protein and neutrophil extracellular traps are associated with periodontitis severity in patients with rheumatoid arthritis: A pilot case-control study.

OBJECTIVES: An interrelationship between rheumatoid arthritis (RA) and periodontitis has been suggested due to their common pathogenic mechanisms. Protein carbamylation and neutrophil extracellular traps (NETs) formation have been shown to be related to autoimmune conditions, including RA, but their association with periodontitis has not been elucidated. Therefore, we assessed whether or not circulating levels of carbamylated protein (CarP) and NETs are associated with periodontitis severity and influenced by periodontal treatment. METHODS: We conducted a retrospective case-control study that included 40 patients with RA and periodontitis, 30 patients with periodontitis, and 43 systemically and periodontally healthy controls to assess the circulating levels of CarP and NETs and rheumatologic and periodontal conditions. The same assessments were also performed in 22 patients with RA and periodontitis after 2 months of periodontal treatment, including oral hygiene instruction and full-mouth supragingival scaling. RESULTS: Patients with RA and periodontitis showed significantly higher serum levels of CarP and NETs than the control group (P = 0.04 and P < 0.001, respectively). The serum levels of CarP and NETs were significantly correlated positively with the mean values of probing depth (P = 0.01 and P = 0.007, respectively) and clinical attachment level (P = 0.007 and P = 0.001, respectively) in the 40 patients with RA and periodontitis. Multiple logistic regression analyses also revealed significantly positive associations between the serum levels of CarP and NETs and moderate to severe periodontitis (P = 0.03 and P = 0.001, respectively). Furthermore, periodontal treatment significantly decreased the serum levels of CarP and NETs in patients with RA and periodontitis (P = 0.03 and P = 0.02). CONCLUSION: The circulating levels of CarP and NETs are associated with periodontitis severity and influenced by periodontal treatment in patients with RA.

The number of remaining teeth as a risk indicator of cognitive impairment: A cross-sectional clinical study in Sado Island.

Most studies that have demonstrated an association between number of remaining teeth and cognitive impairment have treated teeth as a continuous variable, although the relationship is nonlinear. The aim of this cross-sectional study was to determine the critical number of remaining teeth in hospital outpatients at which the association with cognitive impairment becomes apparent. Japanese adults living on Sado Island who visited Sado General Hospital were invited to participate in Project in Sado for Total Health. In total, 2,530 adults were interviewed and had their teeth counted; 1,476 of these individuals also completed the Mini-Mental State Examination (MMSE) and underwent measurement of their serum high-sensitivity C-reactive protein (hsCRP) levels. Patients on dialysis and those with hsCRP ≥ 10 mg/L were excluded. The final study group consisted of 565 adults (290 men and 275 women) of mean age 69.8 (range 29-91) years. An MMSE score < 24 was considered to indicate cognitive impairment. The subjects were categorized according to whether they had an edentulous jaw or one to 10, 11-20, 21-27, or ≥28 remaining teeth. One hundred twenty-eight of the 565 study participants were diagnosed to have cognitive impairment. Multiple logistic regression analysis revealed associations of cognitive impairment with older age, ischemic heart disease, smoking, and alcohol consumption. After adjustment for covariates, having one to 10 remaining teeth was significantly associated with cognitive impairment. There is a significant association between having only one to 10 remaining teeth and cognitive impairment in hospital outpatients.

Relationship between renal function and periodontal disease in community-dwelling elderly women with different genotypes.

OBJECTIVES: The aim of this study was to examine the association between periodontal disease and renal function in elderly women with different genotypes. MATERIAL AND METHODS: A total of 332 postmenopausal never-smoking women were analysed. Poor renal function was defined as serum cystatin C > 0.91 mg/l. Periodontal disease markers such as periodontal inflamed surface area (PISA) were evaluated. Selected variables, including PISA quartile, body mass index (BMI), HbA1C and age in Arg allele carriers and non-carriers based on the beta-3 adrenergic receptor, or between Ala allele carriers and non-carriers based on peroxisome proliferator-activated receptor gamma, were analysed using multiple logistic regression analysis. RESULTS: The odds ratios of serum cystatin C level and PISA (fourth quartile) were significantly positive for both Arg (2.52; p = 0.035) and Ala allele non-carriers (2.36; p = 0.021). A significant association was also found between serum cystatin C level and BMI for both Arg (1.18; p = 0.001) and Ala allele non-carriers (1.12; p = 0.003). CONCLUSION: The results of this study suggest that periodontal inflammation might be associated with renal function. Furthermore, in both the Arg and Ala allele non-carriers, the associations between BMI and PISA for renal function became stronger.

PPARγ gene polymorphism, C-reactive protein level, BMI and periodontitis in post-menopausal Japanese women.

BACKGROUND: Several studies have reported inconsistent results regarding the association between the PPARγPro12Ala polymorphism and obesity. Obese individuals had higher C-reactive protein (CRP) levels compared with those of normal weight, and PPARγ activation could significantly reduce serum high-sensitive CRP level. We have previously suggested that the Pro12Ala polymorphism represents a susceptibility factor for periodontitis, which is a known risk factor for increased CRP level. OBJECTIVES: The aim was to investigate associations between PPARγ gene polymorphism, serum CRP level, BMI and/or periodontitis among post-menopausal Japanese women. MATERIALS AND METHODS: The final sample in this study comprised 359 post-menopausal Japanese women. Periodontal parameters, including PD, CAL and BOP, were measured per tooth. PPARγPro12Ala genotype was determined by PCR-RFLP. Hs-CRP value was measured by a latex nephelometry assay. RESULTS: No significant differences in age, BMI or periodontal parameters were found between the genotypes. The percentages of sites with PD ≥ 4 mm were significantly higher among the hsCRP ≥ 1 mg/l group than the hsCRP < 1 mg/l group (p = 0.003). Positive correlations were found between serum hsCRP levels and the percentages of sites with PD ≥ 4 mm (p = 0.043) in PPARγ Ala allele carriers, and BMI (p = 0.033) in non-carriers. After adjustment for model covariates, BMI was significantly associated with serum hsCRP level. CONCLUSION: The PPARγPro12Ala polymorphism was not independently associated with periodontitis, serum CRP level or BMI in post-menopausal Japanese women. However, serum hsCRP level correlated with periodontitis in Ala allele carriers, and with BMI in non-carriers.

The Interaction Between ß-3 Adrenergic Receptor and Peroxisome Proliferator-Activated Receptor Gamma Gene Polymorphism to Periodontal Disease in Community-Dwelling Elderly Japanese.

BACKGROUND: It has been hypothesized that ß-3 adrenergic receptor and peroxisome proliferator-activated receptor gamma (PPARγ) might have gene-environmental and gene-gene interactions in periodontal disease. The purpose of this study is to elucidate the interaction between ß-3 adrenergic receptor and PPARγ gene polymorphism with periodontal disease. METHODS: Three hundred thirty-two postmenopausal females were enrolled, and their serum high-sensitivity C-reactive protein (hsCRP) and hemoglobin A1c (HbA1c) were examined. ß-3 adrenergic receptor and PPARγ genotypes were then determined. An oral examination was performed. The number of remaining teeth was counted, and the probing depth (PD) and clinical attachment level (CAL) were measured. Prevalence-rate ratios (PRRs) were calculated by multiple Poisson regression analyses to evaluate the relationship among periodontal disease markers, such as the number of sites with CAL 4 to 5 or ≥6 mm or PD 4 to 5 or ≥6 mm, and ß-3 adrenergic receptor polymorphisms, PPARγ polymorphisms, and the interaction term adjusted by age, hsCRP, and HbA1c, after converting the number of remaining teeth (n) to an offset variable. RESULTS: In the participants with body mass index (BMI) ≥25, PRRs of ß-3 adrenergic receptor genotype (Trp/Arg and Arg/Arg) for periodontal disease markers were 0.13 to 0.70 (P <0.0001 to 0.74), those of PPARγ genotype (Pro/Pro) were 0.66 to 3.14 (P = 0.01 to 0.68), and those of the interaction term for the two genotypes were 1.69 to 12.61 (P <0.0001 to 0.33). However, in the participants with BMI <25, a constant tendency was not observed. CONCLUSION: The results confirmed a positive relationship between the interaction term for ß-3 adrenergic receptor genotype and PPARγ genotype and various periodontal markers in obese elderly females.

The interaction between beta-3 adrenergic receptor polymorphism and obesity to periodontal disease in community-dwelling elderly Japanese.

OBJECTIVES: The purpose of this study was to elucidate whether the association between beta-3 adrenergic receptor polymorphism and periodontal disease is modified by body weight. MATERIAL AND METHODS: We enrolled 332 postmenopausal women and determined their HbA1C levels (%) and beta-3 adrenergic receptor (rs4994) genotypes. Periodontal parameters including clinical attachment level (CAL) were measured. After selecting subjects for each body mass index (BMI) level, the prevalence rate ratio (PRR) by multiple Poisson regression analysis was calculated to evaluate the relationship between periodontal disease and beta-3 adrenergic receptor polymorphism. The number of sites with CAL≥6 mm was used as a dependent variable, and beta-3 adrenergic receptor genotype [categorized as Arg non-carriers (reference) or Arg carriers], age (y) and HbA1C (%) were adopted as independent variables. We converted the number of probing sites (n) to an offset variable. RESULTS: The PRR of the beta-3 adrenergic receptor genotype for the number of sites of CAL≥6 mm showed a positive association in subjects with BMI≥25.0 and increased markedly with BMI. The PRR in subjects with BMI≥30 was 3.10 (p < 0.0001). CONCLUSION: This study indicates a positive association between periodontal disease and the beta-3 adrenergic receptor genotype in obese individuals.

Profiling biomarkers in gingival crevicular fluid using multiplex bead immunoassay.

OBJECTIVE: Biomarkers in gingival crevicular fluid (GCF) have been investigated; however, measurements were limited by the small sample volume available. The aim of this study was to determine the levels of 40 different cytokines and chemokines in GCF samples. DESIGN: Eleven patients with generalised chronic periodontitis participating in a supportive periodontal therapy programme with remaining probing pocket depths (PDs) of >5mm were enrolled. One healthy and two diseased sites were sampled in each subject. Forty biomarkers in GCF were examined using a multiplex bead immunoassay. Porphyromonas gingivalis from the diseased sites was quantified by real-time polymerase chain reaction. RESULTS: Twenty-six biomarkers were detected in the GCF samples using the multiplex bead immunoassay. The levels of nine biomarkers were significantly different between the diseased and healthy sites after adjustment with Bonferroni's correction. The level of 26 biomarkers in diseased sites was compared between bleeding on probing (BOP)-positive and BOP-negative sites. Interleukin (IL)-1ß and interferon-inducible protein (IP)-10 levels were significantly higher in BOP-positive diseased sites than BOP-negative diseased sites after adjustment for multiple comparisons (IL-1ß, p=0.0007, IP-10; p=0.0009). In addition, the levels of IL-1ß in GCF were found to be strongly correlated with the P. gingivalis ratio (r=0.646, p=0.0012). CONCLUSION: IL-1ß levels in GCF correlate with the PDs, BOP and the presence of P. gingivalis in subgingival plaque. Multiplex bead assays can be useful in GCF studies. These findings can help in identifying new diagnostic methods in the diagnosis of periodontal disease.

Immunoregulatory gene polymorphisms in Japanese women with preterm births and periodontitis.

Many studies have reported an association between periodontal disease and preterm birth, although this remains controversial. Cytokines and antibodies produced to give resistance to infection can enter the bloodstream and cause preterm labor. We analyzed maternal genetic polymorphisms in various immunoregulatory genes that could affect both preterm birth and periodontitis. A total of 1099 women referred to the Department of Obstetrics and Gynecology, Niigata University Medical and Dental Hospital were candidates for participation, 424 of whom refused, and 553 were excluded. The final number of subjects was 122 (51 with preterm birth, 71 with term birth). Genomic DNA was isolated from venous blood, and 22 polymorphisms were determined: IL-1A, IL-1B, IL-1RN, IL-2, IL-4, IL-6, IL-10, TNFA, TNFRI, TNFRII, FcγRIIA, FcγRIIB, FcγRIIIA, FcγRIIIB, and FcαR. Within five days of labor, periodontal parameters were evaluated, and bacteria from subgingival plaque were detected using real-time PCR. There was no difference in the prevalence and degree of periodontitis between term and preterm births. Chi-squared tests showed that an age <33 years and FcαR(+56)T/C alleles were associated with preterm birth. Multiple logistic regression analysis represented a model with significant fitness in which four variables were associated with preterm birth: maternal age, number of Aggregatibacter actinomycetemcomitans, IL-6(-572)G/C, and FcαR(+56)T/C. In conclusion, there was no association between preterm birth and periodontitis in this study. A. actinomycetemcomitans, IL-6, and FcαR were suggested to be associated with preterm birth. Multiple logistic regression models with both genetic and environmental factors would be useful for evaluating susceptibility to preterm birth.

The association of Aggregatibacter actinomycetemcomitans with preeclampsia in a subset of Japanese pregnant women.

AIM: To determine whether periodontitis and three prominent members of the periodontal flora are associated with the development of preeclampsia (hypertension plus proteinuria) Materials and Methods: The samples were composed of 127 systemically healthy women. Within 5 days after labour, clinical periodontal parameters and Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis and Prevotella intermedia in subgingival plaque were evaluated. Maternal serum IgG antibody specific for each bacteria was determined by enzyme-linked immunosorbent assay. Multivariate logistic regression analysis was used to control for confounders (maternal age, body mass index before pregnancy, parity, and smoking). RESULTS: Eighteen women were affected with preeclampsia. The number of A.actinomycetemcomitans was shown to be significantly associated with preeclampsia in the logistic regression model (odds ratio; 1.7, 95% confidence interval; 1.1­2.7). There were statistically significant differences between the preeclamptic and control groups in body mass index before pregnancy, pre-term birth and low birthweight (respectively, p = 0.014, p = 0.010 and p < 0.0001). We found no statistically significant association between preeclampsia and periodontal clinical parameters or the presence of periodontitis. CONCLUSION: In systemically healthy pregnant women, our findings suggested that the levels of maternal subgingival A. actinomycetemcomitans DNA were elevated in preeclamptic women.

Peroxisome proliferator-activated receptor gamma polymorphism and periodontitis in pregnant Japanese women.

BACKGROUND: Recent studies suggest an association between maternal periodontitis and preterm birth, although the association remains controversial. It was suggested that mechanisms such as a genetic predisposition for a hyperinflammatory response cause periodontitis and preterm births. Peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear hormone receptor and ligand-dependent transcription factor. PPARgamma inhibits the transcriptional activity of the genes that produce proinflammatory mediators and repress periodontitis. Recently, a common polymorphism, proline(PRO)-to-alanine(ALA) mutation at codon12 in exonB (Pro12Ala: rs 1801282) PPARgamma, was reported to reduce the ability to transactivate responsive promoters. In this study, we tested whether the PPARgammaPro12Ala polymorphism was associated with maternal periodontitis and/or preterm birth. METHODS: Genomic DNA was isolated from the venous blood of pregnant Japanese women (term birth: n = 72; preterm birth: n = 58). The PPARgammaPro12Ala genotype was determined by polymerase chain reaction (PCR)-restriction fragment length polymorphism. Within 5 days after labor, clinical periodontal parameters were evaluated, and periodontopathic bacteria from the subgingival plaque were detected by species-specific PCR. RESULTS: The mean clinical attachment level (P = 0.012), mean probing depth (P = 0.031), mean gingival index (P = 0.037), and percentages of sites with bleeding on probing (P = 0.041) in women with the PPARgammaPro12Ala genotype were significantly higher than in women with the PPARgammaPro12Pro genotype. However, there was no association between preterm birth and periodontitis. CONCLUSION: We suggest that the PPARgammaPro12Ala polymorphism may represent a genetic susceptibility factor for the clinical measurements of periodontitis in a limited number of pregnant Japanese women, but it probably cannot influence the relationship between periodontitis and preterm birth.

The effect of periodontal treatment on serum leptin, interleukin-6, and C-reactive protein.

BACKGROUND: Previous studies suggest that periodontitis is closely related to obesity and metabolic syndrome. Leptin, a pleiotrophic hormone produced by adipose tissue, has been reported to be related to periodontitis. This study investigates the effects of periodontal treatment on the serum levels of leptin and other cytokines in patients with chronic periodontitis (CP). METHODS: Serum samples were taken from 33 CP patients (22 non-smokers, 11 smokers) and 18 healthy subjects. The serum leptin, adiponectin, tumor necrosis factor-alpha, interleukin (IL)-6, and C-reactive protein (CRP) levels were measured before and after non-surgical periodontal treatment. RESULTS: Significant differences between healthy and CP patients were found in serum leptin, IL-6, and CRP levels (P = 0.0018, P = 0.0064, and P = 0.0095, respectively). The serum leptin level was associated with mean probing depth, mean clinical attachment level, mean alveolar bone loss, and body mass index. There were significant associations between serum leptin levels and IL-6 and CRP levels. After non-surgical periodontal treatment, serum leptin, IL-6, and CRP levels were significantly decreased (mean +/- SD before and after, P value, respectively: leptin, 8.02 +/- 5.5, 7.10 +/- 4.4, P = 0.015; IL-6, 1.73 +/- 1.02, 1.36 +/- 0.73, P = 0.048; and CRP, 802.0 +/- 1065, 491.2 +/- 479.3, P = 0.047). CONCLUSIONS: Periodontal treatment is effective in reducing serum leptin, IL-6, and CRP levels. The results suggest that leptin, IL-6, and CRP could be mediating factors that connect metabolic syndrome and periodontitis.

Antibody responses to Porphyromonas gingivalis outer membrane protein in the first trimester.

BACKGROUND: Porphyromonas gingivalis (Pg) is one of the most harmful periodontal pathogens and it has been reported that Pg is associated with preterm birth (PTB), intrauterine growth retardation (IUGR) and pregnancy-induced hypertension (PIH), discovered by animal experiments and clinical research. The relationship between adverse pregnancy outcomes and maternal antibody response to Pg is controversial. On the other hand, the serum C-reactive protein (CRP) has been recognised as a reliable serum marker of periodontal disease. AIMS: To determine the significance of antibody responses to Pg affecting pregnancy outcomes in the first trimester. METHODS: A case-control study was carried out on women with PTB (n = 58), IUGR (n = 91), PIH (n = 32) and without any complications (control, n = 98). The serum level of the CRP and IgG1 against 40-kDa outer membrane protein of Pg (anti-40-kDa OMP Pg-IgG1) in the first trimester was measured. RESULTS: The IUGR group, and PTB patients whose placentas were diagnosed as chorioamnionitis or whose vaginal flora included Lactobacilli, showed a lower level of anti-40-kDa OMP Pg-IgG1 than the control group. There was no difference in the serum CRP level between each case group and control group. CONCLUSIONS: These results suggest that a lack of humoral immunity against Pg in early pregnancy is associated with IUGR and some PTB.