| 1. |
- Bengtsson, Viveca Wallin, et al.
(författare)
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Periodontitis related to cardiovascular events and mortality : a long-time longitudinal study
- 2021
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Ingår i: Clinical Oral Investigations. - : Springer Science and Business Media Deutschland GmbH. - 1432-6981 .- 1436-3771. ; 25:6, s. 4085-4095
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The present study assessed if individuals ≥ 60 years of age with periodontitis are more likely to develop stroke or ischemic heart diseases, or at a higher risk of death for 17 years. Material and methods: At baseline individuals ≥ 60 received a dental examination including a panoramic radiograph. Periodontitis was defined as having ≥ 30% sites with ≥ 5-mm distance from the cementoenamel junction to the marginal bone level. Medical records were annually reviewed from 2001 to 2018. Findings from the medical records identifying an ICD-10 code of stroke and ischemic heart diseases or death were registered. Results: Associations between periodontitis and incidence of ischemic heart disease were found in this 17-year follow-up study in all individuals 60–93 years (HR: 1.5, CI: 1.1–2.1, p = 0.017), in women (HR: 2.1, CI: 1.3–3.4, p = 0.002), and in individuals 78–96 years (HR: 1.7, CI: 1.0–2.6, p = 0.033). Periodontitis was associated with mortality in all individuals (HR: 1.4, CI: 1.2–1.8, p = 0.002), specifically in men (HR: 1.5, CI: 1.1–1.9, p = 0.006) or in ages 60–72 years (HR: 2.2, CI: 1.5–3.2, p = 0.000). Periodontitis was more prevalent among men (OR: 1.8, CI: 1.3–2.4, p = 0.000). Conclusions: Individuals with periodontitis have an increased risk for future events of ischemic heart diseases and death. Clinical relevance: Improving periodontal health in older individuals may reduce overall mortality and ischemic heart diseases. Both dental and medical professionals should be aware of the associations and ultimately cooperate. © 2021, The Author(s).
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| 2. |
- Halldén, Christer, et al.
(författare)
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Origin of Swedish hemophilia B mutations
- 2013
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 11:11, s. 2001-2008
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Tidskriftsartikel (refereegranskat)abstract
- Background More than 1100 mutations that cause hemophilia B (HB) have been identified. At the same time, specific F9 mutations are present at high frequencies in certain populations, which raise questions about the origin of HB mutations. ObjectivesTo describe the mutation spectrum of all HB families in Sweden and investigate if mutations appearing in several families are due to independent recurrent mutations (RMs) or to a common mutation event (i.e. are identical by descent (IBD)). Patients/MethodsThe registered Swedish HB population consists of patients from 86 families. Mutations were identified by resequencing and identical haplotypes were defined using 74 markers and a control population of 285 individuals. The ages of IBD mutations were estimated using ESTIAGE. ResultsOut of 77 presumably unrelated patients with substitution mutations, 47 patients (61%) had mutations in common with other patients. Haplotyping of the 47 patients showed that 24 patients had IBD mutations (51%) with estimated ages of between two and 23 generations. A majority of these patients had mild disease. Eight of the 15 mutations observed in more than one family were C>T transitions in CpG sites and all eight were RMs. ConclusionsThe association of IBD mutations with a mild phenotype is similar to what has been previously observed in hemophilia A. Noteworthy features of the mutations that are common to more than one family are the equal proportions of patients with RM and IBD mutations and the correlation between the occurrence of RMs and C>T transitions at CpG sites.
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| 3. |
- Manderstedt, Eric, et al.
(författare)
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Genetic variation of the blood coagulation regulator tissue factor pathway inhibitor and venous thromboembolism among middle-aged and older adults: A population-based cohort study
- 2022
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Ingår i: Research and practice in thrombosis and haemostasis. - : Elsevier BV. - 2475-0379. ; 6:7
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Tidskriftsartikel (refereegranskat)abstract
- Background: Tissue factor is the main initiator of blood coagulation, and tissue factor pathway inhibitor (TFPI) is the primary inhibitor of the initiation of blood coagulation. The genetic variation of TFPI and the relation to venous thromboembolism (VTE), that is, venous thrombosis and pulmonary embolism, remains to be clarified. This exome sequencing study aimed to determine the molecular epidemiology of the TFPI gene and the relation to VTE in a large population-based cohort of middle-aged and older adults. Methods: The exomes of TFPI were analyzed for variants in 28,794 subjects without previous VTE (born 1923–1950, 60% women), who participated in the Malmö Diet and Cancer Study (1991–1996). Patients were followed until the first event of VTE, death, or 2018. Qualifying variants were defined as loss-of-function or nonbenign (PolyPhen-2) missense variants with minor allele frequency less than 0.1%. Results: No common variant was associated with VTE. Nine rare variants (two loss-of-function and seven nonbenign missense) were classified as qualifying and included in collapsing analysis. Prevalence of qualifying variants was 0.09%. Five individuals with VTE compared to 17 individuals without VTE carried one qualifying variant. Cox multivariate regression analysis adjusted for age, sex, body mass index, systolic blood pressure, smoking and alcohol consumption, rs6025, rs1799963, and ancestry showed a hazard ratio of 2.9 (95% CI, 1.2–7.1) for rare qualifying variants. Conclusion: Rare qualifying TFPI variants were associated with VTE, suggesting that rare variants in TFPI contribute to the development of VTE. The qualifying TFPI gene variants were very rare, suggesting a constrained gene. © 2022 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH).
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| 4. |
- Mäntylä, Päivi, et al.
(författare)
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Subgingival Aggregatibacter actinomycetemcomitans associates with the risk of coronary artery disease
- 2013
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Ingår i: Journal of Clinical Periodontology. - : Blackwell Munksgaard. - 0303-6979 .- 1600-051X. ; 40:6, s. 583-590
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Tidskriftsartikel (refereegranskat)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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| 5. |
- Widen, Cecilia, et al.
(författare)
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Systemic inflammatory impact of periodontitis on acute coronary syndrome
- 2016
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Ingår i: Journal of Clinical Periodontology. - : Wiley. - 0303-6979 .- 1600-051X. ; 43:9, s. 713-719
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Tidskriftsartikel (refereegranskat)abstract
- AimA causative relationship between acute coronary syndrome (ACS) and periodontitis has yet to be defined. The aim of this study was to assess differences in levels of serum cytokines between individuals with or without ACS or periodontal comorbidity. Material and MethodsIn a case-control study, individuals with ACS (78 individuals, 10.3% females) and matching healthy controls (78 individuals, 28.2% females) were included. Medical and dental examinations were performed to diagnose ACS and periodontitis. Serum levels of cytokines were assessed, using Luminex technology. ResultsA diagnosis of periodontitis in the ACS and control group was diagnosed in 52.6% and 12.8% of the individuals, respectively. The unadjusted odds-ratio that individuals with ACS also had periodontitis was 7.5 (95% CI: 3.4, 16.8, p<0.001). Independent of periodontal conditions, individuals with ACS had significantly higher serum levels of IL8 (mean: 44.3 and 40.0pg/ml) and vascular endothelial growth factor (VEGF) (mean: 82.3 and 55.3pg/ml) than control individuals. A diagnosis of periodontitis made no difference in serum cytokine expressions. ConclusionElevated serum levels of VEGF were associated with ACS. Serum cytokine expression in individuals with ACS is unrelated to periodontal conditions.
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| 6. |
- Halldén, Christer, et al.
(författare)
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Small and large PROS1 deletions but no other types of rearrangements detected in patents with protein S deficiency
- 2012
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Ingår i: Thrombosis and Haemostasis. - : Georg Thieme Verlag. - 0340-6245. ; 108:1, s. 94-100
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Tidskriftsartikel (refereegranskat)abstract
- Protein S deficiency is a dominantly inherited disorder that results from mutations in the PROS] gene. Previous sequencing of the gene failed to detect mutations in eight out of 18 investigated Swedish families, whereas segregation analyses detected large deletions in three out of the eight families. The present study investigates more thoroughly for the presence of deletions but also for other types of rearrangements. FISH analysis confirmed the existence of the three previously identified large deletions, but failed to identify any other type of rearrangement among the eight analysed families. MLPA analysis of the PROS1 gene revealed two smaller deletions covering two and four exons, respectively. Thus, deletions could be found in five out of eight families where no point mutations could be found despite sequencing of the gene. Twelve additional, not previously analysed, families were subsequently analysed using MLPA. The analysis identified two smaller deletions (3 and 4 exons). Including all PS-deficient families, i.e. also the 10 families where sequencing found a causative point mutation, deletions were identified in seven out of 30 PS-deficient families. A strategy of sequencing followed by MLPA analysis in mutation-negative families identified the causative mutation in 15 out of 18 of Swedish PS-deficient families. Most deletions were different as determined by their sizes, locations and flanking haplotypes. FISH (8 families) and MLPA analysis (20 families) failed to identify other types of rearrangements.
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| 7. |
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| 8. |
- Johansson, Anna, et al.
(författare)
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Large deletions of the PROS1 gene in a large fraction of mutationnegative patients with protein S deficiency
- 2005
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Ingår i: Thrombosis and Haemostasis. - : Georg Thieme Verlag. - 0340-6245. ; 94:5, s. 951-957
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Tidskriftsartikel (refereegranskat)abstract
- Protein S deficiency is an autosomal dominant disorder that results from mutations in the PROS I gene. Conventional mutation detection techniques fail to detect a pathogenic PROSI mutation in approximately 50% of cases. The present study investigates whether large deletions of PROS I are found in families where mutations in the PROS I gene have not been found despite sequencing. For this purpose, a dense set of SNP and microsatellite markers were used in segregation analysis to identify deletions. Large deletions were identified by this technique in three out of eight investigated families (38%). The deletions en-compassed at least 35 kb, 437 kb and 449 kb respectively. The deletions were confirmed by quantitative PCR. Haplotype analysis showed that the three large deletions and the five other disease haplotypes were all different. All of the eight disease haplotypes co-segregated with protein S deficiency, but each of the five non-deletion haplotypes were present also in normal individuals. In conclusion: Large deletions of PROS I are relatively common in protein S deficiency patients and screening for large deletions in PROS I mutation-negative individuals are therefore warranted.
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| 9. |
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| 10. |
- Manderstedt, Eric, et al.
(författare)
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Classic Thrombophilias and Thrombotic Risk Among Middle-Aged and Older Adults : A Population-Based Cohort Study
- 2022
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Ingår i: Journal of the American Heart Association. - : Wiley-Blackwell Publishing Ltd. - 2047-9980. ; 11:4
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Five classic thrombophilias have been recognized: factor V Leiden (rs6025), the prothrombin G20210A variant (rs1799963), and protein C, protein S, and antithrombin deficiencies. This study aimed to determine the thrombotic risk of classic thrombophilias in a cohort of middle-aged and older adults. METHODS AND RESULTS: Factor V Leiden, prothrombin G20210A and protein-coding variants in the PROC (protein C), PROS1 (protein S), and SERPINC1 (antithrombin) anticoagulant genes were determined in 29 387 subjects (born 1923–1950, 60% women) who participated in the Malmö Diet and Cancer study (1991–1996). The Human Gene Mutation Database was used to define 68 disease-causing mutations. Patients were followed up from baseline until the first event of venous thromboembolism (VTE), death, or Dec 31, 2018. Carriership (n=908, 3.1%) for disease-causing mutations in the PROC, PROS1, and SERPINC1 genes was associated with incident VTE: Hazard ratio (HR) was 1.6 (95% CI, 1.3–1.9). Variants not in Human Gene Mutation Database were not linked to VTE (HR, 1.1; 95% CI, 0.8–1.5). Heterozygosity for rs6025 and rs1799963 was associated with incident VTE: HR, 1.8 (95% CI, 1.6–2.0) and HR, 1.6 (95% CI, 1.3–2.0), respectively. The HR for carrying 1 classical thrombophilia variant was 1.7 (95% CI, 1.6–1.9). HR was 3.9 (95% CI, 3.1–5.0) for carriers of ≥2 thrombophilia variants. CONCLUSIONS: The 5 classic thrombophilias are associated with a dose-graded risk of VTE in middle-aged and older adults. Disease-causing variants in the PROC, PROS1, and SERPINC1 genes were more common than the rs1799963 variant but the conferred genetic risk was comparable with the rs6025 and rs1799963 variants.
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