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- Sliz, E., et al.
(författare)
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Evidence of a causal effect of genetic tendency to gain muscle mass on uterine leiomyomata
- 2023
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)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. |
- Liukkonen, J, et al.
(författare)
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Salivary biomarkers in association with periodontal parameters and the periodontitis risk haplotype
- 2018
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Ingår i: Innate immunity. - : SAGE Publications. - 1753-4267 .- 1753-4259. ; 24:7, s. 439-447
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Tidskriftsartikel (refereegranskat)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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| 3. |
- Akhi, R, et al.
(författare)
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Salivary IgA to MAA-LDL and Oral Pathogens Are Linked to Coronary Disease
- 2019
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Ingår i: Journal of dental research. - : SAGE Publications. - 1544-0591 .- 0022-0345. ; 98:3, s. 296-303
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Tidskriftsartikel (refereegranskat)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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| 4. |
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| 5. |
- Liukkonen, J, et al.
(författare)
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Immunological and Microbiological Profiling of Cumulative Risk Score for Periodontitis
- 2020
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Ingår i: Diagnostics (Basel, Switzerland). - : MDPI AG. - 2075-4418. ; 10:8
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Tidskriftsartikel (refereegranskat)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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