| 1. |
- Sliz, E., et al.
(author)
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Evidence of a causal effect of genetic tendency to gain muscle mass on uterine leiomyomata
- 2023
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1
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Journal article (peer-reviewed)abstract
- Uterine leiomyomata (UL) are the most common tumours of the female genital tract and the primary cause of surgical removal of the uterus. Genetic factors contribute to UL susceptibility. To add understanding to the heritable genetic risk factors, we conduct a genome-wide association study (GWAS) of UL in up to 426,558 European women from FinnGen and a previous UL meta-GWAS. In addition to the 50 known UL loci, we identify 22 loci that have not been associated with UL in prior studies. UL-associated loci harbour genes enriched for development, growth, and cellular senescence. Of particular interest are the smooth muscle cell differentiation and proliferation-regulating genes functioning on the myocardin-cyclin dependent kinase inhibitor 1A pathway. Our results further suggest that genetic predisposition to increased fat-free mass may be causally related to higher UL risk, underscoring the involvement of altered muscle tissue biology in UL pathophysiology. Overall, our findings add to the understanding of the genetic pathways underlying UL, which may aid in developing novel therapeutics.
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| 2. |
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| 3. |
- Kurki, MI, et al.
(author)
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FinnGen provides genetic insights from a well-phenotyped isolated population
- 2023
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 613:7944, s. 508-
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Journal article (peer-reviewed)abstract
- Population isolates such as those in Finland benefit genetic research because deleterious alleles are often concentrated on a small number of low-frequency variants (0.1% ≤ minor allele frequency < 5%). These variants survived the founding bottleneck rather than being distributed over a large number of ultrarare variants. Although this effect is well established in Mendelian genetics, its value in common disease genetics is less explored1,2. FinnGen aims to study the genome and national health register data of 500,000 Finnish individuals. Given the relatively high median age of participants (63 years) and the substantial fraction of hospital-based recruitment, FinnGen is enriched for disease end points. Here we analyse data from 224,737 participants from FinnGen and study 15 diseases that have previously been investigated in large genome-wide association studies (GWASs). We also include meta-analyses of biobank data from Estonia and the United Kingdom. We identified 30 new associations, primarily low-frequency variants, enriched in the Finnish population. A GWAS of 1,932 diseases also identified 2,733 genome-wide significant associations (893 phenome-wide significant (PWS), P < 2.6 × 10–11) at 2,496 (771 PWS) independent loci with 807 (247 PWS) end points. Among these, fine-mapping implicated 148 (73 PWS) coding variants associated with 83 (42 PWS) end points. Moreover, 91 (47 PWS) had an allele frequency of <5% in non-Finnish European individuals, of which 62 (32 PWS) were enriched by more than twofold in Finland. These findings demonstrate the power of bottlenecked populations to find entry points into the biology of common diseases through low-frequency, high impact variants.
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| 4. |
- Divaris, K., et al.
(author)
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Phenotype Harmonization in the GLIDE2 Oral Health Genomics Consortium
- 2022
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In: Journal of Dental Research. - : Sage Publications. - 0022-0345 .- 1544-0591. ; 101:11, s. 1408-1416
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Journal article (peer-reviewed)abstract
- Genetic risk factors play important roles in the etiology of oral, dental, and craniofacial diseases. Identifying the relevant risk loci and understanding their molecular biology could highlight new prevention and management avenues. Our current understanding of oral health genomics suggests that dental caries and periodontitis are polygenic diseases, and very large sample sizes and informative phenotypic measures are required to discover signals and adequately map associations across the human genome. In this article, we introduce the second wave of the Gene-Lifestyle Interactions and Dental Endpoints consortium (GLIDE2) and discuss relevant data analytics challenges, opportunities, and applications. In this phase, the consortium comprises a diverse, multiethnic sample of over 700,000 participants from 21 studies contributing clinical data on dental caries experience and periodontitis. We outline the methodological challenges of combining data from heterogeneous populations, as well as the data reduction problem in resolving detailed clinical examination records into tractable phenotypes, and describe a strategy that addresses this. Specifically, we propose a 3-tiered phenotyping approach aimed at leveraging both the large sample size in the consortium and the detailed clinical information available in some studies, wherein binary, severity-encompassing, and “precision,” data-driven clinical traits are employed. As an illustration of the use of data-driven traits across multiple cohorts, we present an application of dental caries experience data harmonization in 8 participating studies (N = 55,143) using previously developed permanent dentition tooth surface–level dental caries pattern traits. We demonstrate that these clinical patterns are transferable across multiple cohorts, have similar relative contributions within each study, and thus are prime targets for genetic interrogation in the expanded and diverse multiethnic sample of GLIDE2. We anticipate that results from GLIDE2 will decisively advance the knowledge base of mechanisms at play in oral, dental, and craniofacial health and disease and further catalyze international collaboration and data and resource sharing in genomics research.
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| 5. |
- Pradhan-Palikhe, Pratikshya, et al.
(author)
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Subgingival bacterial burden in relation to clinical and radiographic periodontal parameters.
- 2013
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In: Journal of periodontology. - 1943-3670. ; 84:12, s. 1809-1817
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Journal article (peer-reviewed)abstract
- BACKGROUND: This cross-sectional study characterizes the association between subgingival bacterial profile and periodontal parameters in patients assigned to coronary angiography because of cardiologic problems, which may affect the oral microbiota.METHODS: Pooled subgingival bacterial samples were collected from 477 dentate individuals during the oral examinations, along with periodontal probing depth (PD) and assessments of bleeding on probing (BOP) and radiographic alveolar bone loss (ABL). The checkerboard DNA-DNA hybridization assay was used to determine the levels of 29 oral bacteria, which were divided into three bacterial complexes.RESULTS: All bacterial combinations from the etiologic bacterial group and each species from the red complex were significantly associated (P <0.001) with grade of ABL. The prevalence of the etiologic bacterial group and the level of each species were also associated strongly with the proportion of sites with PD 4 to 5 mm and ≥ 6 mm, BOP, and ABL, except Aggregatibacter actinomycetemcomitans. Levels of Gram-negative oral bacteria correlated significantly with those of Gram-positive species (r = 0.840, P <0.001). In multiple logistic regression analysis, the prevalence of the etiologic bacterial group, levels of Gram-negative bacteria and Treponema denticola, and the prevalence of Porphyromonas gingivalis and T. denticola associated significantly with ABL, whereas other bacterial complexes and levels of Gram-positive species did not.CONCLUSIONS: Although levels of Gram-negative and -positive species paralleled periodontal parameters, only the species considered etiologic were associated with ABL.
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| 6. |
- Buhlin, K., et al.
(author)
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Periodontal treatment influences risk markers for atherosclerosis in patients with severe periodontitis
- 2009
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In: Atherosclerosis. - : Elsevier. - 0021-9150 .- 1879-1484. ; 206:2, s. 518-522
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Journal article (peer-reviewed)abstract
- This study investigated the effect of mechanical infection control for periodontitis and periodontal surgery on the prevalence of well-established risk factors for atherosclerosis, and plasma levels of cytokines, antibodies against heat shock proteins and markers of systemic inflammation. Sixty-eight patients between 39 and 73 years of age with severe periodontitis who had been referred to four specialist periodontology clinics in Sweden were investigated. A fasting venous blood sample was taken at baseline and additional samples were collected after 3 and 12 months. A total of 54 patients underwent periodontal treatment. The periodontal treatment was successful, as pathogenic gingival pockets decreased significantly. Plasma glucose, lipids and markers of systemic inflammation were not significantly altered after 3 months. One year after the initial treatment, HDL-C concentrations were significantly increased (Δ0.08 mmol/L) whereas LDL-C concentrations decreased (Δ0.23 mmol/L). Haptoglobin concentrations were also lower. Interleukin-18 and interferon-γ levels were also lower after 12 months (60 ng/L (-23%) and 11 ng/L (-97%) respectively). Treatment had no effect on plasma levels of IgA, IgG1, IgG2 antibodies against heat shock proteins. In conclusion, this study indicates that standard treatment for periodontal disease induces systemic changes in several biochemical markers that reflect the risk for atherosclerosis.
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| 7. |
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| 8. |
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| 9. |
- Liuba, P., et al.
(author)
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Matrix Metalloproteinase-8 Activity is Increased in Type 1 Diabetes Children with High-Risk Diabetes HLA and Systemic Inflammation
- 2012
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In: Cardiology in the Young. - 1467-1107. ; 22:S1, s. 115-116
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Conference paper (peer-reviewed)abstract
- Background: Matrix metalloproteinases (MMPs) and myeloperoxidase (MPO) are colocalized to lipid-laden macrophages, and play a central role in initiation and propagation of chronic vascular diseases including atherosclerosis. Prior cross-sectional studies from our centre on children and adolescents with type 1 diabetes suggested possible propensity conferred by diabetes-risk HLA DQ2/8, particularly in an inflammatory milieu, to peripheral vascular dysfunction, an important precursor of atherosclerosis. In the same population, we aimed to assess whether this putative interplay between DQ2/8 and inflammation also reflects into increased activity of MMP and MPO. Methods: Blood pressure, inflammatory, lipid, HbA1c, cyclic guanilate monophospate (cGMP), along with degree of exposure to secondhand tobacco smoke (STS) were determined in 74 children and adolescents with type 1 diabetes at baseline and 1 year later. MMP-8 and MPO levels were measured only at the 2nd time-point. Results: In univariate regression, baseline BMI, HbA1c, CRP(log), and TC/HDL were all predictors of 1-year MMP-2 (p,.05 for all), while exposure to STS, BMI, cGMP, and TC/ HDL predicted levels of MPO (p,.05 for all). The rise in serum MMP-8 was most increased in those with both DQ2/8 and CRP .1 mg/l (p=0.01), but no such difference was noted with regard to MPO. Conclusion: In young patients with type 1 diabetes, increased activities of MMP and MPO appear to relate mainly to dyslipidemia, but inflammation, particularly in those with diabetes-risk HLA, and exposure to tobacco smoke could be important stimuli as well.
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| 10. |
- Liukkonen, J, et al.
(author)
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Immunological and Microbiological Profiling of Cumulative Risk Score for Periodontitis
- 2020
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In: Diagnostics (Basel, Switzerland). - : MDPI AG. - 2075-4418. ; 10:8
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Journal article (peer-reviewed)abstract
- The cumulative risk score (CRS) is a mathematical salivary diagnostic model to define an individual’s risk of having periodontitis. In order to further validate this salivary biomarker, we investigated how periodontal bacteria, lipopolysaccharide (LPS), and systemic and local host immune responses relate to CRS. Subgingival plaque, saliva, and serum samples collected from 445 individuals were used in the analyses. Plaque levels of 28 microbial species, especially those of Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Porphyromonas endodontalis, Prevotella intermedia, and Tannerella forsythia, and serum and salivary levels of IgA and IgG against these five species were determined. Additionally, LPS activity was measured. High CRS associated strongly with all IgA/IgG antibody and LPS levels in saliva, whereas in serum the associations were not that obvious. In the final logistic regression model, the best predictors of high CRS were saliva IgA burden against the five species (OR 7.04, 95% CI 2.25–22.0), IgG burden (3.79, 1.78–8.08), LPS (2.19, 1.38–3.47), and the sum of 17 subgingival Gram-negative species (6.19, 2.10–18.3). CRS is strongly associated with microbial biomarker species of periodontitis and salivary humoral immune responses against them.
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| 11. |
- Mäntylä, Päivi, et al.
(author)
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Subgingival Aggregatibacter actinomycetemcomitans associates with the risk of coronary artery disease
- 2013
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In: Journal of Clinical Periodontology. - 0303-6979 .- 1600-051X. ; 40:6, s. 583-590
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Journal article (peer-reviewed)abstract
- Aim We investigated the association between angiographically verified coronary artery disease (CAD) and subgingival Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia and Treponema denticola. Materials and Methods The cross-sectional study population (n = 445) comprised 171 (38.4%) patients with Stable CAD, 158 (35.5%) with acute coronary syndrome (ACS) and 116 (26.1%) with no significant CAD (No CAD). All patients participated in clinical and radiological oral health examinations. Pooled subgingival bacterial samples were analysed by checkerboard DNA–DNA hybridization assays. Results In all study groups, the presence of P. gingivalis, T. forsythia and T. denticola indicated a significant (p ≤ 0.001) linear association with the extent of alveolar bone loss (ABL), but A. actinomycetemcomitans did not (p = 0.074). With a threshold level of bacterial cells 1 × 105 A. actinomycetemcomitans was significantly more prevalent in the Stable CAD group (42.1%) compared to the No CAD group (30.2%) (p = 0.040). In a multi-adjusted logistic regression analysis using this threshold, A. actinomycetemcomitans positivity associated with Stable CAD (OR 1.83, 95% CI 1.00–3.35, p = 0.049), but its level or levels of other bacteria did not. Conclusions The presence of subgingival A. actinomycetemcomitans associates with an almost twofold risk of Stable CAD independently of alveolar bone loss.
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| 12. |
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| 13. |
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| 14. |
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| 15. |
- Akhi, R, et al.
(author)
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Salivary IgA to MAA-LDL and Oral Pathogens Are Linked to Coronary Disease
- 2019
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In: Journal of dental research. - : SAGE Publications. - 1544-0591 .- 0022-0345. ; 98:3, s. 296-303
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Journal article (peer-reviewed)abstract
- A large body of literature has established the link between periodontal disease and cardiovascular disease. Oxidized low-density lipoproteins (OxLDLs) have a crucial role in atherosclerosis progression through initiation of immunological response. Monoclonal IgM antibodies to malondialdehyde-modified low-density lipoprotein (MDA-LDL) and to malondialdehyde acetaldehyde–modified low-density lipoprotein (MAA-LDL) have been shown to cross-react with the key virulence factors of periodontal pathogens Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. We have previously shown that salivary IgA antibodies to MAA-LDL cross-react with P. gingivalis in healthy humans. In this study, we aim to assess whether oral mucosal immune response represented by salivary IgA to MAA-LDL and oral pathogens is associated with coronary artery disease (CAD). Also, the molecular mimicry through antibody cross-reaction between salivary IgA to MAA-LDL and oral pathogens was evaluated. The study subjects consisted of 451 patients who underwent a coronary angiography with no CAD ( n = 133), stable CAD ( n = 169), and acute coronary syndrome (ACS, n = 149). Elevated salivary IgA antibody levels to MAA-LDL, Rgp44 (gingipain A hemagglutinin domain of P. gingivalis), and Aa-HSP60 (heat shock protein 60 of A. actinomycetemcomitans) were discovered in stable-CAD and ACS patients when compared to no-CAD patients. In a multinomial regression model adjusted for known cardiovascular risk factors, stable CAD and ACS were associated with IgA to MAA-LDL ( P = 0.016, P = 0.043), Rgp44 ( P = 0.012, P = 0.004), Aa-HSP60 ( P = 0.032, P = 0.030), Tannerella forsythia ( P = 0.002, P = 0.004), Porphyromonas endodontalis ( P = 0.016, P = 0.020), Prevotella intermedia ( P = 0.038, P = 0.005), and with total IgA antibody concentration ( P = 0.002, P = 0.016). Salivary IgA to MAA-LDL showed cross-reactivity with the oral pathogens tested in the study patients. The study highlights an association between salivary IgA to MAA-LDL and atherosclerosis. However, whether salivary IgA to MAA-LDL and the related oral humoral responses play a causal role in the development in the CAD should be elucidated in the future.
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| 16. |
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| 17. |
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| 18. |
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| 19. |
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| 20. |
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| 21. |
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| 22. |
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| 23. |
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| 24. |
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| 25. |
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| 26. |
- Liljestrand, JM, et al.
(author)
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Association of Endodontic Lesions with Coronary Artery Disease
- 2016
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In: Journal of dental research. - : SAGE Publications. - 1544-0591 .- 0022-0345. ; 95:12, s. 1358-1365
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Journal article (peer-reviewed)abstract
- An endodontic lesion (EL) is a common manifestation of endodontic infection where Porphyromonas endodontalis is frequently encountered. EL may associate with increased risk for coronary artery disease (CAD) via similar pathways as marginal periodontitis. The aim of this cross-sectional study was to delineate the associations between EL and CAD. Subgingival P. endodontalis, its immune response, and serum lipopolysaccharide were examined as potential mediators between these 2 diseases. The Finnish Parogene study consists of 508 patients (mean age, 62 y) who underwent coronary angiography and extensive clinical and radiographic oral examination. The cardiovascular outcomes included no significant CAD ( n = 123), stable CAD ( n = 184), and acute coronary syndrome (ACS; n = 169). EL was determined from a panoramic tomography. We combined data of widened periapical spaces (WPSs) and apical rarefactions to a score of EL: 1, no EL ( n = 210); 2, ≥1 WPS per 1 apical rarefaction ( n = 222); 3, ≥2 apical rarefactions ( n = 76). Subgingival P. endodontalis was defined by checkerboard DNA-DNA hybridization analysis, and corresponding serum antibodies were determined by ELISA. In our population, 50.4% had WPSs, and 22.8% apical rarefactions. A total of 51.2% of all teeth with apical rarefactions had received endodontic procedures. Subgingival P. endodontalis levels and serum immunoglobulin G were associated with a higher EL score. In the multiadjusted model (age, sex, smoking, diabetes, body mass index, alveolar bone loss, and number of teeth), having WPSs associated with stable CAD (odds ratio [OR] = 1.94, 95% confidence interval [95% CI] = 1.13 to 3.32, P = 0.016) and highest EL score were associated with ACS (OR = 2.46, 95% CI = 1.09 to 5.54, P = 0.030). This association was especially notable in subjects with untreated teeth with apical rarefactions ( n = 59, OR = 2.72, 95% CI = 1.16 to 6.40, P = 0.022). Our findings support the hypothesis that ELs are independently associated with CAD and in particular with ACS. This is of high interest from a public health perspective, considering the high prevalence of ELs and CAD.
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| 27. |
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| 28. |
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| 29. |
- Liukkonen, J, et al.
(author)
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Salivary biomarkers in association with periodontal parameters and the periodontitis risk haplotype
- 2018
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In: Innate immunity. - : SAGE Publications. - 1753-4267 .- 1753-4259. ; 24:7, s. 439-447
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Journal article (peer-reviewed)abstract
- Genetic factors play a role in periodontitis. Here we examined whether the risk haplotype of MHC class III region BAT1-NFKBIL1-LTA and lymphotoxin-α polymorphisms associate with salivary biomarkers of periodontal disease. A total of 455 individuals with detailed clinical and radiographic periodontal health data were included in the study. A 610 K genotyping chip and a Sequenom platform were used in genotyping analyses. Phospholipid transfer protein activity, concentrations of lymphotoxin-α, IL-8 and myeloperoxidase, and a cumulative risk score (combining Porphyromonas gingivalis, IL-1β and matrix metalloproteinase-8) were examined in saliva samples. Elevated IL-8 and myeloperoxidase concentrations and cumulative risk scores associated with advanced tooth loss, deepened periodontal pockets and signs of periodontal inflammation. In multiple logistic regression models adjusted for periodontal parameters and risk factors, myeloperoxidase concentration (odds ratio (OR); 1.37, P = 0.007) associated with increased odds for having the risk haplotype and lymphotoxin-α concentration with its genetic variants rs2857708, rs2009658 and rs2844482. In conclusion, salivary levels of IL-8, myeloperoxidase and cumulative risk scores associate with periodontal inflammation and tissue destruction, while those of myeloperoxidase and lymphotoxin-α associate with genetic factors as well.
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| 30. |
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| 31. |
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| 32. |
- Odermarsky, M., et al.
(author)
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Human Leucocyte Antigen, Infections and Systemic Inflammatory Biomarkers in Early Atherosclerosis in Children and Adolescents with Type 1 Diabetes
- 2015
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In: Cardiology in the Young. - 1467-1107. ; 25:Suppl. 1, s. 33-33
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Conference paper (peer-reviewed)abstract
- Background: This prospective study focuses on factors associated with arterial damage in children with type 1 diabetes (T1D). Materials and Methods: Eighty children and adolescents with T1D (mean age 15, range: 8-20 yrs; mean diabetes duration 7, range: 0.5 to 19 years) were investigated twice, approximately 2 years apart, for carotid artery intima-media thickness (cIMT) and compliance (CAC), flow-mediated dilatation (FMD) of the brachial artery, and plasma levels of matrix metalloproteinase (MMP)-8. HLA genotypes were determined in dried spots of peripheral blood by polymerase chain reaction followed by hybridization assay. The number of respiratory tract infections (RTI) during the past year was obtained by a questionnaire in 56 patients. Results: cIMT progression (% change of cIMT from baseline) correlated inversely with the % changes of both CAC (p = 0.04, r=−0.3, n=62) and FMD (p=0.03, r=−0.3, n=67). RTI frequency correlated significantly with cIMT progression irre- spective of age, diabetes duration, BMI, and HbA1c (p=0.03, r=0.3, in multivariate analysis). When patients were divided in relation to DQ2/8 genotype and RTI, the association of DQ2/8 with cIMT progression remained significant in patients with over three infections/year (p = 0.04, r = 0.3). During follow-up, the group of DQ2/8 patients with CRP > 1 mg/l showed significantly higher levels of plasma MMP-8 than the non-DQ2/8 group. Conclusions: Diabetes-risk genotype DQ2/8 and inflammation con- tribute to vascular changes in children and adolescents with T1D.
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| 33. |
- Oittinen, J, et al.
(author)
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Periodontal disease and bacterial vaginosis increase the risk for adverse pregnancy outcome.
- 2005
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In: Infectious diseases in obstetrics and gynecology. - 1064-7449 .- 1098-0997. ; 13:4, s. 213-216
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Journal article (peer-reviewed)abstract
- OBJECTIVES: To determine whether periodontal disease or bacterial vaginosis (BV) diagnosed before pregnancy increase the risk for adverse pregnancy outcome. METHODS: We enrolled a total of 252 women who had discontinued contraception in order to become pregnant. The first 130 pregnant women were included in the analyses. RESULTS: Multivariate analysis showed a strong association between periodontal disease and adverse pregnancy outcome (OR 5.5, 95% confidence interval 1.4-21.2; p = 0.014), and a borderline association between BV and adverse pregnancy outcome (OR 3.2, 95% confidence interval 0.9-10.7; p = 0.061). CONCLUSION: Our study suggests that pre-pregnancy counseling should include both oral and vaginal examinations to rule out periodontal disease and BV. This may ultimately have an impact on antenatal healthcare, and decrease the risk for adverse pregnancy outcome.
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| 34. |
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| 35. |
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| 36. |
- Palikhe, A, et al.
(author)
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Lymphotoxin alpha LTA+496C allele is a risk factor for periodontitis in patients with coronary artery disease.
- 2008
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In: Tissue Antigens. - : Wiley. - 0001-2815 .- 1399-0039. ; 71:6, s. 530-7
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Journal article (peer-reviewed)abstract
- Periodontitis and coronary artery disease (CAD) are inflammatory diseases and associated with each other. The major histocompatibility complex (MHC) region carries genes involved in immune response and inflammation. We investigated whether the MHC genes correlate with the presence of periodontitis or with the occurrence of periodontal pathogens in patients with CAD. Blood and saliva samples from CAD patients (n = 106) were collected at the time of hospitalization. Nine MHC genetic markers [human leukocyte antigen (HLA)-A, HLA-B, HLA-DRB1, lymphotoxin alpha (LTA) +253(a/g), +496(C/T), +633(c/g), +724(C/A), C4A and C4B)] were typed. Based on panoramic tomography, patients were categorized into nonperiodontitis and periodontitis groups. Two major periodontal pathogens, Aggregatibacter (Actinobacillus) actinomycetemcomitans and Porphyromonas gingivalis, were cultivated and polymerase chain reaction-amplified from salivary samples. Serum immunoglobulin (Ig)A and IgG antibody levels to these pathogens were measured. In the univariate analysis, LTA+496C allele (OR = 5.29; 95% CI = 2.07-13.51, P = 0.00027), and the occurrence of P. gingivalis in saliva (OR = 4.74; 95% CI = 1.64-13.70; P = 0.002) were more frequent in periodontitis when compared with nonperiodontitis. Similarly, serum IgA antibody level against the pathogen was increased in periodontitis (P = 0.048). In the multiple logistic regression analysis, when a wide range of covariates was included, the LTA+496C allele (OR = 10.87; 95% CI = 3.23-36.60; P = 0.00012) and the elevated serum IgA antibody level against P. gingivalis (OR = 1.56; 95% CI = 1.05-2.30; P = 0.026) remained as significant risk factors for periodontitis. In conclusion, the major finding of this study is that the LTA+496C allele is associated with periodontitis in patients with CAD.
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| 37. |
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| 38. |
- Pussinen, PJ, et al.
(author)
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Antibodies to periodontal pathogens and stroke risk.
- 2004
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In: Stroke; a journal of cerebral circulation. - 1524-4628. ; 35:9, s. 2020-2023
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Journal article (peer-reviewed)abstract
- BACKGROUND AND PURPOSE: The association between cerebrovascular events and periodontitis has been found in few studies based on clinical periodontal examinations. However, evidence on the association between periodontal pathogens and stroke is lacking. Therefore, the aim of the study was to investigate whether elevated levels of serum antibodies to major periodontal pathogens predict stroke in a case-control study. METHODS: The study population comprised 6950 subjects (aged 45 to 64 years) who participated in the Mobile Clinic Health Survey in 1973 to 1976 in Finland. During a follow-up of 13 years, a total of 173 subjects had a stroke. From these, 64 subjects had already experienced a stroke or had signs of coronary heart disease (CHD) at baseline, whereas 109 subjects were apparently healthy. Two controls per case were matched for age, gender, municipality, and disease status. Serum IgG and IgA class antibody levels to the periodontal pathogens, Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis, were determined by multiserotype enzyme-linked immunosorbent assay. RESULTS: The cases identified during the follow-up that were free of stroke or CHD at baseline were more often IgA-seropositive for A. actinomycetemcomitans than were their controls, 41.3% versus 29.3%. Compared with the seronegative, the seropositive subjects had a multivariate odds ratio of 1.6 (95% CI, 1.0 to 2.6) for stroke. The patients with a history of stroke or CHD at baseline were more often IgA-seropositive for P. gingivalis than were their controls, 79.7% versus 70.2%. When compared with the seronegative, the seropositive subjects had an odds ratio of 2.6 (1.0 to 7.0) for secondary stroke. CONCLUSIONS: The present prospective study provides serological evidence that an infection caused by major periodontal pathogens is associated with future stroke.
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| 39. |
- Pussinen, PJ, et al.
(author)
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Antibodies to periodontal pathogens are associated with coronary heart disease.
- 2003
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In: Arteriosclerosis, thrombosis, and vascular biology. - 1524-4636. ; 23:7, s. 1250-1254
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Journal article (peer-reviewed)abstract
- OBJECTIVE: We analyzed the association of coronary heart disease (CHD) and serology of periodontitis in a random sample (n=1163) of men (aged 45 to 74 years) by determining serum IgG-antibodies to Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis. METHODS AND RESULTS: CHD (n=159) was more prevalent among edentulous than dentate subjects (19.8% and 12.1%, P=0.003). In the dentate population, CHD was more common among subjects seropositive for P. gingivalis compared with those seronegative (14.0% and 9.7%, P=0.029). Accordingly, CHD was more prevalent in subjects with a high combined antibody response than those with a low response (17.4% and 11.1%, P=0.026). When adjusted for age and several CHD risk factors, the subjects with a high combined antibody response had an odds ratio of 1.5 (95% CI, 0.95 to 2.50, P=0.077) for prevalent CHD. In a linear regression model, the combined antibody response was directly associated with prevalent CHD (P=0.046) and inversely with serum HDL cholesterol concentration (P=0.050). CONCLUSIONS: In conclusion, edentulousness and serum antibodies to major periodontal pathogens were associated with CHD. This suggests that periodontal infection or response of the host against the infection may play a role in the pathogenesis of CHD.
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| 40. |
- Pussinen, PJ, et al.
(author)
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High serum antibody levels to Porphyromonas gingivalis predict myocardial infarction.
- 2004
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In: European Journal of Cardiovascular Prevention & Rehabilitation. - 1741-8267 .- 1741-8275. ; 11:5, s. 408-411
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Journal article (peer-reviewed)abstract
- BACKGROUND: An association between coronary heart disease (CHD) and clinically diagnosed periodontitis has been found in several epidemiological studies. However, seroepidemiologic evidence based on prospective data on this association is totally lacking. DESIGN: The aim of the study was to investigate serum antibodies to major periodontal pathogens for their prediction of myocardial infarction (MI) in men free of CHD at baseline. METHODS: Cases and controls were ascertained from a random population sample of 4255 men aged 30 to 59 years at baseline. The study cases included 63 men with nonfatal MI or coronary death within the follow-up time of 10 years. Age-matched control subjects (n=63) were randomly chosen from the same cohort. Serum antibody levels to two major periodontopathogenic bacteria, Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis, were determined. RESULTS: There was no significant association between the risk for MI and IgG- or IgA-class antibody levels to A. actinomycetemcomitans or IgG-class antibody levels to P. gingivalis. However, a high P. gingivalis IgA-class antibody level predicted MI independently of classical cardiovascular risk factors. The risk for MI increased by increasing quartiles of antibody levels (P for the trend 0.021). Compared with the first quartile, the multivariate odds ratios of MI in the second, third and fourth quartiles were 2.47 (95% CI 0.75-8.11), 3.30 (1.03-10.58) and 3.99 (1.22-13.10), respectively. CONCLUSION: The study provides serological evidence that an infection caused by the periodontal pathogen, P. gingivalis, increases the risk for MI.
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- Pussinen, PJ, et al.
(author)
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Periodontitis is associated with a low concentration of vitamin C in plasma.
- 2003
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In: Clinical and Diagnostic Laboratory Immunology. - 1071-412X. ; 10:5, s. 897-902
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Journal article (peer-reviewed)abstract
- This study aimed to clarify how concentrations of vitamin C in plasma relate to the serology of periodontitis. The random sample used comprised 431 men, 194 from Finland and 237 from Russia. The plasma vitamin C concentration was determined by o-phtaldialdehyde-fluorometry, and serum immunoglobulin G antibodies to Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis were determined by a multiserotype enzyme-linked immunosorbent assay (ELISA). The mean plasma vitamin C concentration was higher (P < 0.001) in Finnish subjects (mean +/- standard deviation, 4.5 +/- 2.8 mg/liter) than in Russian subjects (1.4 +/- 1.8 mg/liter). Mean antibody levels to both A. actinomycetemcomitans (4.7 +/- 3.6 versus 5.2 +/- 3.1 ELISA units [P = 0.05]) and P. gingivalis (5.7 +/- 2.5 versus 7.6 +/- 2.9 ELISA units [P < 0.001]) were lower in Finnish men than in Russian men. In the combined Finnish and Russian population, the antibody levels to P. gingivalis were negatively correlated with vitamin C concentrations (r = -0.22; P < 0.001); this association remained statistically significant (P = 0.010) in a linear regression model after adjustment for confounding factors. The proportion of P. gingivalis-seropositive subjects decreased with increasing vitamin C concentrations (P for trend, <0.01), but no trend was seen among A. actinomycetemcomitans-seropositive subjects. In conclusion, P. gingivalis infection is associated with low concentrations of vitamin C in plasma, which may increase colonization of P. gingivalis or disturb the healing of the infected periodontium.
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| 47. |
- Vilkuna-Rautiainen, T, et al.
(author)
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Serum antibody response to periodontal pathogens and herpes simplex virus in relation to classic risk factors of cardiovascular disease.
- 2006
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In: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 35:6, s. 1486-1494
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Journal article (peer-reviewed)abstract
- BACKGROUND: Increasing evidence links chronic infections, especially burden of several infections, with increased risk for cardiovascular diseases (CVD). We studied joint immune response against two major periodontal pathogens and herpes simplex virus (HSV) in relation to established risk factors of CVD. METHODS: Serum antibody levels to HSV, Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis were determined by ELISA. The study included 1107 subjects, 734 from Finland and 373 from Russia. RESULTS: Combined antibody response to periodontal pathogens was associated inversely (OR, 95% CI) with high-density lipoprotein (HDL) cholesterol concentration (beta = 0.35; 0.20, 0.60; P < 0.001) and directly with HSV antibody quartiles: compared with the first quartile, ORs (95% CI) for quartiles 2-4 were 1.43 (0.88-2.32), 1.74 (1.07-2.82), and 1.89 (1.18-3.02), respectively (P for trend <0.001), after adjusting for age, gender, area, education, smoking, BMI, alcohol, triglycerides, and number of teeth. In linear regression analysis, the 3-pathogen antibody score (comprising antibody levels against periodontal pathogens and HSV) was inversely associated with HDL cholesterol concentration (beta = -0.067/1 mmol/l; -0.235, -0.018; P < 0.05). CONCLUSIONS: HSV infection may promote infection by periodontal pathogens. Furthermore, the infectious burden comprising HSV and periodontitis may increase the risk for CVD by clearly decreasing HDL cholesterol concentrations.
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