Advertisement

Association of systemic beta-defensin-1 and -20G/A DEFB1 gene polymorphism with Behçet's disease

  • Amani Kallel
    Affiliations
    University of Tunis El Manar, Faculty of Medicine of Tunis, LR99ES11 Tunis, Tunisia

    Rabta Hospital, Laboratory of Biochemistry, Jebbari 1007, Tunis, Tunisia.
    Search for articles by this author
  • Author Footnotes
    1 These authors contributed equally to the work.
    Thouraya Ben Salem
    Footnotes
    1 These authors contributed equally to the work.
    Affiliations
    University of Tunis El Manar, Faculty of Medicine of Tunis, LR99ES11 Tunis, Tunisia

    Rabta Hospital, Service of Internal Medicine, Jebbari 1007, Tunis, Tunisia.
    Search for articles by this author
  • Author Footnotes
    1 These authors contributed equally to the work.
    Mohamed Bassem Hammami
    Footnotes
    1 These authors contributed equally to the work.
    Affiliations
    University of Tunis El Manar, Faculty of Medicine of Tunis, LR99ES11 Tunis, Tunisia

    Rabta Hospital, Laboratory of Biochemistry, Jebbari 1007, Tunis, Tunisia.
    Search for articles by this author
  • Fatma Said
    Affiliations
    University of Tunis El Manar, Faculty of Medicine of Tunis, LR99ES11 Tunis, Tunisia

    Rabta Hospital, Service of Internal Medicine, Jebbari 1007, Tunis, Tunisia.
    Search for articles by this author
  • Riadh Jemaa
    Affiliations
    University of Tunis El Manar, Faculty of Medicine of Tunis, LR99ES11 Tunis, Tunisia

    Rabta Hospital, Laboratory of Biochemistry, Jebbari 1007, Tunis, Tunisia.
    Search for articles by this author
  • Mohamed Habib Houman
    Affiliations
    University of Tunis El Manar, Faculty of Medicine of Tunis, LR99ES11 Tunis, Tunisia

    Rabta Hospital, Service of Internal Medicine, Jebbari 1007, Tunis, Tunisia.
    Search for articles by this author
  • Moncef Feki
    Correspondence
    Corresponding author at: Rabta Hospital, Laboratory of Biochemistry, 1007 jebbari, Tunis, Tunisia.
    Affiliations
    University of Tunis El Manar, Faculty of Medicine of Tunis, LR99ES11 Tunis, Tunisia

    Rabta Hospital, Laboratory of Biochemistry, Jebbari 1007, Tunis, Tunisia.
    Search for articles by this author
  • Author Footnotes
    1 These authors contributed equally to the work.
Published:February 26, 2019DOI:https://doi.org/10.1016/j.ejim.2019.02.008

      Highlights

      • Circulating human beta defensin-1 is increased in Behcet's disease.
      • Circulating human beta defensin-1 is independently associated with Neuro-Behcet.
      • The A allele of the DFEB1 -20G/A polymorphism is associated with Behcet's disease.

      Abstract

      Background

      Behçet's disease (BD) is a multisystem inflammatory disease of unknown etiology. Beta-defensins are antimicrobial peptides involved in epithelial host defense. To explore whether beta-defensins might be involved in BD pathogenesis, we examined plasma human beta-defensin-1 (hBD-1) and DEFB1 -20G/A polymorphism in BD patients.

      Methods

      This case-control study included 106 BD patients fulfilling the criteria of the International Study Group for BD and 156 controls. The -20G/A genotypes were determined by PCR-RFLP analysis in all participants, and plasma hBD-1 was assessed by ELISA in 77 BD patients and 44 controls, only. Stepwise multiple regression models were applied to determine independent predictors for plasma hBD-1 in BD patients.

      Results

      Distribution of -20G/A genotypes was different between BD patients and controls. Compared to GG genotype, “GA” genotype [OR (95% CI), 3.12 (1.56–6.16); p = .001] and “AA” genotype [2.57 (1.10–5.96); p = .027)] were associated with increased risk for BD. Plasma hBD-1 concentrations were significantly higher in BD patients than controls (9.81 ± 3.52 ng/mL vs. 5.30 ± 3.02 ng/mL; p < .001), and in BD patients with neurological involvement than those without (11.1 ± 4.12 ng/mL vs. 9.19 ± 3.10 ng/mL; p = .040). No variation was noted according to other clinical features, treatment received or -20G/A genotypes. In multivariate analysis, neurological involvement was the only predictor for plasma hBD-1 (β, 0.274; p = .029).

      Conclusions

      Findings suggest that hBD-1 and its encoding gene DEFB1 could modulate the risk for BD, especially for BD neurological involvement. Further work is needed for a better understanding of role of hBD-1 and its genetic variants in the pathogenesis of BD.

      Abbreviations:

      BD (Behcet's disease), hBD-1 (human beta-defensin-1)

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to European Journal of Internal Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Yazici H.
        • Seyahi E.
        • Hatemi G.
        • Yazici Y.
        Behçet syndrome: a contemporary view.
        Nat Rev Rheumatol. 2018; 14: 107-119
        • International Study Group for Behçet's disease
        Criteria for diagnosis of Behçet's disease.
        Lancet. 1990; 335: 1078-1080
        • Davatchi F.
        • Assaad-Khalil S.
        • Calamia K.T.
        • Crook J.E.
        • Sadeghi-Abdollahi B.
        • Schirmer M.
        • et al.
        International team for the revision of the international criteria for Behçet's disease (ITR-ICBD). The international criteria for Behçet's disease (ICBD): a collaborative study of 27 countries on the sensitivity and specificity of the new criteria.
        J Eur Acad Dermatol Venereol. 2013; 28: 338-347
        • Mahr A.
        • Maldini C.
        Epidemiology of Behçet's disease.
        Rev Med Interne (Paris). 2014; 35: 81-89
        • Houman M.H.
        • Bel Feki N.
        Pathophysiology of Behçet's disease.
        Rev Med Interne (Paris). 2014; 35: 90-96https://doi.org/10.1016/j.revmed.2013.10.012
        • Greco A.
        • De Virgilio A.
        • Ralli M.
        • Ciofalo A.
        • Mancini P.
        • Attanasio G.
        • et al.
        Behçet's disease: new insights into pathophysiology, clinical features and treatment options.
        Autoimmun Rev. 2018; 17: 567-575https://doi.org/10.1016/j.autrev.2017.12.006
        • Yurdakul S.
        • Hamuryudan V.
        • Yazici H.
        Behcet syndrome.
        Curr Opin Rheumatol. 2004; 16: 38-42
        • Pazgier M.
        • Hoover D.M.
        • Yang D.
        • Lu W.
        • Lubkowski J.
        Human beta-defensins.
        Cell Mol Life Sci. 2006; 63: 1294-1313
        • Huang Y.P.
        • Wang T.Y.
        • Wang W.
        • Sun H.Z.
        Association between genetic polymorphisms in DEFB1 and susceptibility to digestive diseases.
        Med Sci Monit. 2015; 21: 2240-2250
        • Silva O.
        • Porto W.
        • Ribeiro S.
        • Batista I.
        • Franco O.
        Host-Defense peptides and their potential use as biomarkers in human diseases.
        Drug Discov Today. 2018; 23: 1666-1671https://doi.org/10.1016/j.drudis.2018.05.024
        • Goldman M.J.
        • Anderson G.M.
        • Stolzenberg E.D.
        • Kari U.P.
        • Zasloff M.
        • Wilson J.M.
        Human β-defensin-1 is a salt-sensitive antibiotic in the lung that is inactivated in cystic fibrosis.
        Cell. 1997; 88: 553-560
        • Kallsen K.
        • Andersen E.
        • Heine H.
        Histone deacetylase (HDAC)1 controls the expression of beta defensin 1 in human lung epithelial cells.
        PloS One. 2012; 7: e50000https://doi.org/10.1371/journal.pone.0050000
        • Bogefors J.
        • Kvarnhammar A.M.
        • Höckerfelt U.
        • Cardell L.O.
        Reduced tonsillar expression of human β-defensin 1, 2 and 3 in allergic rhinitis.
        FEMS Immunol Med Microbiol. 2012; 65: 431-438https://doi.org/10.1111/j.1574-695X.2012.00959.x
        • Schaefer A.S.
        • Richter G.M.
        • Nothnagel M.
        • Laine M.L.
        • Ruhling A.
        • Schafer C.
        • et al.
        A 3’ UTR transition within DEFB1 is associated with chronic and aggressive periodontitis.
        Genes Immun. 2010; 11: 45-54https://doi.org/10.1038/gene.2009.75
        • Zaitseva M.A.
        • Bragvadze B.G.
        • Svitich O.A.
        • Namazova-Baranova L.S.
        • Gankovskaya L.V.
        Analysis of TLRs genes expression and DEFB1 polymorphisms association in children with bronchial asthma.
        Bull RSMU. 2016; : 39-43
        • Abiko Y.
        • Nishimura M.
        • Kaku T.
        Defensins in saliva and the salivary glands.
        Med Electron Microsc. 2003; 36: 247-252
        • Miller S.A.
        • Dykes D.D.
        • Polesky H.F.
        A simple salting out procedure for extracting DNA from human nucleated cells.
        Nucleic Acids Res. 1988; 11: 1215
        • Prado-Montes de Oca E.
        • Rangel-Villalobos H.
        • Gallegos-Arreola M.P.
        • Sandoval L.
        • Figuera L.E.
        SNPs in human beta-defensin 1 gene (DEFB1): frequencies in a Mexican population and new PCR-RFLPs assays.
        Int J Immunogenet. 2006; 33: 339-342
        • Schneider S.
        • Roessli D.
        • Excoffier L.
        Arlequin Version 2.000: Software for Population Genetics Data Analysis.
        Genetics and Biometry Laboratory, University of Geneva, Switzerland1995-2000
        • Prado-Montes de Oca E.
        • Garcia-Vargas A.
        • Lozano-Inocencio R.
        • Gallegos-Arreola M.P.
        • Sandoval-Ramírez L.
        • Dávalos-Rodríguez N.O.
        • et al.
        Association of β-defensin 1 single nucleotide polymorphisms with atopic dermatitis.
        Int Arch Allergy Immunol. 2007; 142: 211-218
        • Sandrin-Garcia P.
        • Brandão L.A.
        • Guimarães R.L.
        • Pancoto J.A.
        • Donadi E.A.
        • Lima-Filho J.L.
        • et al.
        Functional single-nucleotide polymorphisms in the DEFB1 gene are associated with systemic lupus erythematosus in southern Brazilians.
        Lupus. 2012; 21: 625-631
        • Kocsis A.K.
        • Lakatos P.L.
        • Somogyvári F.
        • Fuszek P.
        • Papp J.
        • Fischer S.
        • et al.
        Association of beta-defensin 1 single nucleotide polymorphisms with Crohn's disease.
        Scand J Gastroenterol. 2008; 43: 299-307
        • Ceren Karahan Z.
        • Biriken D.
        • Boyvat A.
        • Dolapei I.
        • Asku E.
        • Ozenci H.
        Functional polymorphisms and haplotypes of human Beta Defensin 1 (DEFB1) gene in Behcet's disease patients.
        Clin Exp Rheumatol. 2010; 28: S164
        • Hameed A.F.
        • Jaradat S.
        • Al-Musawi B.M.
        • Sharquie K.
        • Ibrahim M.J.
        • Hayani R.K.
        • et al.
        Association of higher defensin beta-4 genomic copy numbers with Behçet's disease in Iraqui patients.
        Sultan Qaboos Univ Med J. 2015; 15: 491-495
        • Park J.J.
        • Oh B.R.
        • Kim J.Y.
        • Park J.A.
        • Kim C.
        • Lee Y.J.
        • et al.
        Copy number variation of β-defensin genes in Behçet's disease.
        Clin Exp Rheumatol. 2011; 29 (Suppl 67): S20-S23
        • Kaltsa G.
        • Bamias G.
        • Siakavellas S.I.
        • Goukos D.
        • Karagiannakis D.
        • Zampeli E.
        • et al.
        Systemic levels of human β-defensin 1 are elevated in patients with cirrhosis.
        Ann Gastroenterol. 2016; 29: 63-70
        • Williams W.M.
        • Torres S.
        • Siedlak S.L.
        • Castellani R.J.
        • Perry G.
        • Smith M.A.
        • et al.
        Antimicrobial peptide β-defensin-1 expression is upregulated in Alzheimer's brain.
        J Neuroinflammation. 2013; 10127https://doi.org/10.1186/1742-2094-10-127
        • Sahasrabudhe K.S.
        • Kimball J.R.
        • Morton T.H.
        • Weinberg A.
        • Dale B.A.
        Expression of the antimicrobial peptide, human beta-defensin 1, in duct cells of minor salivary glands and detection in saliva.
        J Dent Res. 2000; 79: 1669-1674
        • Prado-Montes de Oca E.
        Human beta-defensin 1: a restless warrior against allergies, infections and cancer.
        Int J Biochem Cell Biol. 2010; 42: 800-804https://doi.org/10.1016/j.biocel.2010.01.021
        • Polesello V.
        • Zupin L.
        • Di Lenarda R.
        • Biasotto M.
        • Ottaviani G.
        • Gobbo M.
        • et al.
        Impact of DEFB1 gene regulatory polymorphisms on hBD-1 salivary concentration.
        Arch Oral Biol. 2015; 60: 1054-1058https://doi.org/10.1016/j.archoralbio.2015.03.009