Serum, salivary, and tissue levels of plasminogen in familial Mediterranean fever, amyloidosis, and chronic periodontitis

Fentoğlu, Özlem; Dinç, Gözde; Doğru, Atalay; Karahan, Nermin; İlhan, İlter; Kırzıoğlu, Fatma Yeşim; Şentürk, Mehmet Fatih; Orhan, Hikmet

doi:10.1002/jper.17-0243

Cited by 4 publications

(8 citation statements)

References 48 publications

(125 reference statements)

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“…FMF patients with amyloidosis had increased clinical periodontal parameters when compared to FMF patients without amyloidosis and systemically healthy controls. Our findings are supported by a previous report of an intensive inflammatory infiltration in the gingival tissue samples of FMF patients with amyloidosis 28 . The increased levels of t‐PA and uPA, and depleted t‐PA inhibitor leads to a hyperfibrinolytic status in patients with amyloidosis 1 .…”

Section: Discussionsupporting

confidence: 91%

“…Supporting these findings, the serum and salivary levels of PLG were reported to be significantly correlated with the clinical periodontal indices in the FMF group in our previous report 28 . Although there are very limited data on the association between periodontitis and FMF, the presence of a strong relationship between both diseases has been suggested 35–38 .…”

Section: Discussionsupporting

confidence: 61%

“…Third, the MEFV mediated activation of inflammatory pathways leads to an increase in serum acute phase reactants, resulting in periodontal disease. These mechanisms have also been supported by studies reporting higher clinical periodontal indices in patients with FMF 28,41 …”

Section: Discussionmentioning

confidence: 71%

“…The complex R202Q/M694V homozygous state led to an increased risk of periodontitis (Odds Ratio [OR]: 3.6) and FMF‐associated amyloidosis (OR: 7.6) 27 . Moreover, serum and salivary PLG levels have also been shown to be correlated with acute phase reactants such as C‐reactive protein (CRP), SAA, and clinical periodontal parameters in patients with FMF and periodontitis even when amyloid or amyloid‐like deposition in the gingiva is lacking 28 …”

Section: Introductionmentioning

confidence: 99%

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Plasminogen gene polymorphisms [c.924C>T and IVS 8+14 G>A] in periodontitis and familial Mediterranean fever: A case‐control study

Fentoğlu

Tülüceoğlu

Orhan

2021

J of Periodontal Research

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Background and objective The plasminogen (PLG) activation system plays an essential role in severe inflammation based diseases such as periodontitis, destructive membranous periodontal disease (ligneous periodontitis), familial Mediterranean fever (FMF), and amyloidosis. We have aimed to evaluate variations in PLG and the associations between PLG and MEFV genotypes in patients with FMF/ FMF‐related secondary amyloidosis and periodontitis. Material and methods A total of 247 individuals who were either diagnosed with FMF or systemically healthy were recruited to this human observational study with a cross‐sectional design. All individuals were also diagnosed with periodontitis or periodontally healthy. Blood samples were obtained from patients with FMF and systemically healthy controls. Clinical periodontal indicators were recorded. All polymorphisms located in exons 6 and 8 of PLG and mutations located on exons 2 and 10 of the MEFV gene were analyzed by DNA Sanger Sequencing. Genotypes and allele frequencies of PLG and MEFV were detected and tested by the Hardy‐Weinberg equilibrium. Serum levels of amyloid A (SAA), high‐sensitive C‐reactive protein (hs‐CRP), PLG, and salivary PLG levels were determined by using enzyme‐linked immunosorbent assay (ELISA). Results Two polymorphisms were identified in PLG: G to A polymorphism on the 14th nucleotide of intron 8 and C to T polymorphism on the 924th nucleotide of the coding region (IVS 8+14 G>A and c.924C>T, respectively). In IVS 8+14 G>A polymorphisms, wild‐type genotype: GG, heterozygote genotype: GA and homozygote genotype: AA. In c.924C>T polymorphism, wild‐type genotype: CC, heterozygote genotype: CT and homozygote genotype: TT. The frequency of the heterozygous polymorphisms of PLG was significantly increased (17.6%) in FMF patients with periodontitis (p = .027). A large proportion of the test group that was heterozygous for MEFV‐R202Q also had heterozygous PLG polymorphisms. Remarkable exacerbation in periodontal parameters was observed in patients with FMF and amyloidosis. SAA and hs‐CRP levels were significantly correlated with salivary PLG levels in patients with periodontitis and heterozygous PLG. Conclusions The current study describes IVS 8+14 G>A (rs2295368) and c.924C>T (rs1380916375) polymorphisms for the first time in the periodontal literature, which might play an important role in the pathogenesis of periodontitis, FMF, or amyloidosis. The elucidation of PLG polymorphisms is beneficial from a public health perspective by increasing the quality of life in these patients and reducing the mortality and morbidity associated with inflammatory diseases such as periodontal disease, FMF, and FMF‐related amyloidosis.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 61%

Section: Discussionmentioning

confidence: 71%

Section: Introductionmentioning

confidence: 99%

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Plasminogen gene polymorphisms [c.924C>T and IVS 8+14 G>A] in periodontitis and familial Mediterranean fever: A case‐control study

Fentoğlu

Tülüceoğlu

Orhan

2021

J of Periodontal Research

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“…Single nucleotide polymorphism rs6596473 in this gene was associated with aggressive periodontitis in three independent populations of Germans (P = 5 × 10 −3 , OR 1.35, 95% CI 1.10-1.67), after adjusting for smoking and gender 115. Plasminogen activators are involved in plasmin activation, which plays an important role in vascular events and tissue remodeling.Plasminogen has also been found in inflamed gingival and periodontal sites, gingival crevicular fluid, serum, and saliva of patients with periodontitis [116][117][118]. The plasminogen activator 4G/5G singlenucleotide polymorphism in the promoter region of the plasminogen activator inhibitor-1 gene and the Alu-repeat insertion/deletion polymorphism in intron 8 of the tissue plasminogen activator gene was evaluated in a Turkish population of 84 patients with chronic periodontitis and 105 controls.…”

mentioning

confidence: 99%

Periodontal health and disease: The contribution of genetics

Shaddox

Morford

Nibali

2020

Periodontology 2000

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Periodontitis is an infectious, inflammatory disease that is associated with a complex interplay between specific bacteria, host response, and environmental factors. Because of its high degree of familial aggregation, specifically for the more aggressive forms of the disease, genetics factors have been implicated in disease pathogenesis for several decades. This review provides an overview of what we currently know regarding the genetic and epigenetic contributions to periodontal disease and discusses future opportunities in the field.

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A novel plasminogen mutation in a child with hereditary periodic syndrome: A case report

Akbar

Alazami

Alsaleem

et al. 2022

Rheumatology & Autoimmunity

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Introduction: Plasminogen (PLG) deficiency is an ultrarare disease. The reported manifestations in literature were linked to pseudomembrane formation and mucosal surfaces inflammation. Recently, PLG, its activators and its receptors have gained more attention in inflammation regulatory processes, including the release of proinflammatory signaling molecules, and thus its role is believed to have clinical implications beyond what has been known. Case Report: We present a child with recurrent fever who, although managed initially as familial Mediterranean fever, later on, developed a constellation of findings that were not explained by a classified autoinflammatory disease. Genetic testing revealed a novel homozygous PLG mutation (PLG: c.466G>A: p.D156N) and a likely benign heterozygous MEFV gene variant. We propose that the PLG mutation is responsible for the clinical manifestations, which may or may not be exacerbated by the coexistence of the MEFV variant. A relationship between the PLG pathway, inflammation, and FMF severity has been addressed recently in several studies. Conclusion: This report highlights the recently recognized role of the PLG pathway in inflammatory diseases and describes a potentially new presentation of PLG pathogenesis. Further studies are needed to confirm this finding and allow for a more definitive conclusion.

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Serum, salivary, and tissue levels of plasminogen in familial Mediterranean fever, amyloidosis, and chronic periodontitis

Abstract: The PLG system could play an important role in inflammatory diseases, such as chronic periodontitis, FMF, and FMF-associated secondary amyloidosis.

Cited by 4 publications

References 48 publications

Plasminogen gene polymorphisms [c.924C>T and IVS 8+14 G>A] in periodontitis and familial Mediterranean fever: A case‐control study

Plasminogen gene polymorphisms [c.924C>T and IVS 8+14 G>A] in periodontitis and familial Mediterranean fever: A case‐control study

Periodontal health and disease: The contribution of genetics

A novel plasminogen mutation in a child with hereditary periodic syndrome: A case report

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