title: TBX21-1993T/C (rs4794067) polymorphism is associated with increased risk of chronic periodontitis and increased T-bet expression in periodontal lesions, but does not significantly impact the IFN-g transcriptional level or the pattern of periodontophatic bacterial infection.
abstract: Th1-polarized host response, mediated by IFN-γ, has been associated with increased severity of periodontal disease as well as control of periodontal infection. The functional polymorphism TBX21-1993T/C (rs4794067) increases the transcriptional activity of the TBX21 gene (essential for Th1 polarization) resulting in a predisposition to a Th-1 biased immune response. Thus, we conducted a case-control study, including a population of healthy controls (H, n = 218), chronic periodontitis (CP, n = 197), and chronic gingivitis patients (CG, n = 193), to investigate if genetic variations in TBX21 could impact the development of Th1 responses, and consequently influence the pattern of bacterial infection and periodontitis outcome. We observed that the polymorphic allele T was significantly enriched in the CP patients compared to CG subjects, while the H controls demonstrated and intermediate genotype. Also, investigating the putative functionality TBX21-1993T/C in the modulation of local response, we observed that the transcripts levels of T-bet, but not of IFN-γ, were upregulated in homozygote and heterozygote polymorphic subjects. In addition, TBX21-1993T/C did not influence the pattern of bacterial infection or the clinical parameters of disease severity, being the presence/absence of red complex bacteria the main factor associated with the disease status and the subrogate variable probing depth (PD) in the logistic regression analysis.
authors.affiliation: a Departamento de Ciencias Biológicas; Faculdade de Odontologia de Bauru Universidade de São Paulo (FOB/USP) ; Bauru , Brazil.
authors.forename: Franco
authors.initials: F
authors.lastname: Cavalla
authors.forename: Claudia Cristina
authors.initials: CC
authors.lastname: Biguetti
authors.forename: Priscila Maria
authors.initials: PM
authors.lastname: Colavite
authors.forename: Elcia Varise
authors.initials: EV
authors.lastname: Silveira
authors.forename: Walter
authors.initials: W
authors.lastname: Martins
authors.forename: Ariadne
authors.initials: A
authors.lastname: Letra
authors.forename: Ana Paula Favaro
authors.initials: AP
authors.lastname: Trombone
authors.forename: Renato Menezes
authors.initials: RM
authors.lastname: Silva
authors.forename: Gustavo Pompermaier
authors.initials: GP
authors.lastname: Garlet
mesh_terms: D001424:Bacterial Infections / Q000382:microbiology; D058491:Bacterial Load; D016022:Case-Control Studies; D055113:Chronic Periodontitis / Q000235:genetics* / Q000382:microbiology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005891:Gingivitis / Q000235:genetics; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D020825:T-Box Domain Proteins / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation; D000098815:T-bet Transcription Factor
chemical_list: D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D007371:Interferon-gamma
keywords: T-bet; chronic periodontitis; infectogenomics; single nucleotide polymorphism
references.citation: Periodontol 2000. 2014 Feb;64(1):57-80
references.pmid: 24320956
references.citation: J Periodontol. 1991 May;62(5):293-9
references.pmid: 2072240
references.citation: J Periodontol. 2000 Nov;71(11):1699-707
references.pmid: 11128917
references.citation: Infect Immun. 2008 Aug;76(8):3725-34
references.pmid: 18541658
references.citation: J Immunol. 2011 Oct 1;187(7):3821-30
references.pmid: 21890656
references.citation: Bioinformatics. 2006 Aug 1;22(15):1928-9
references.pmid: 16720584
references.citation: Microbes Infect. 2008 Apr;10(5):489-96
references.pmid: 18403243
references.citation: J Endod. 2010 Aug;36(8):1277-88
references.pmid: 20647081
references.citation: Hum Genet. 2005 Jun;117(1):16-26
references.pmid: 15806396
references.citation: J Endod. 2012 Jul;38(7):954-9
references.pmid: 22703660
references.citation: Trends Immunol. 2014 Jan;35(1):3-11
references.pmid: 24269668
references.citation: J Dent Res. 2010 Dec;89(12):1349-63
references.pmid: 20739705
references.citation: J Forensic Odontostomatol. 2000 Jun;18(1):6-9
references.pmid: 11324090
references.citation: Hum Immunol. 2011 Jan;72(1):69-73
references.pmid: 20977921
references.citation: Scand J Immunol. 2011 May;73(5):449-58
references.pmid: 21272048
references.citation: J Dent Res. 2000 Aug;79(8):1548-55
references.pmid: 11023273
references.citation: Scand J Rheumatol. 2010 May;39(3):254-8
references.pmid: 20429676
references.citation: J Periodontal Res. 2009 Aug;44(4):443-51
references.pmid: 18973535
references.citation: J Clin Periodontol. 2009 Sep;36(9):726-38
references.pmid: 19659894
references.citation: PLoS One. 2010;5(4):e10053
references.pmid: 20383335
references.citation: J Clin Periodontol. 2008 Mar;35(3):206-14
references.pmid: 18269660
references.citation: J Allergy Clin Immunol. 2009 May;123(5):1062-8, 1068.e1-8
references.pmid: 19362357
references.citation: Autoimmunity. 2012 Mar;45(2):129-36
references.pmid: 22014209
references.citation: J Periodontol. 2010 Dec;81(12):1814-9
references.pmid: 20681812
references.citation: Nat Genet. 2006 Feb;38(2):209-13
references.pmid: 16415888
references.citation: J Microbiol Methods. 2004 Oct;59(1):117-25
references.pmid: 15325758
references.citation: J Clin Periodontol. 2012 Jul;39(7):608-16
references.pmid: 22582749
references.citation: J Periodontol. 2003 Mar;74(3):391-401
references.pmid: 12710761
references.citation: Periodontol 2000. 2012 Feb;58(1):37-68
references.pmid: 22133366
references.citation: J Periodontal Res. 2014 Dec;49(6):683-95
references.pmid: 24528298
references.citation: J Appl Oral Sci. 2014 Jul-Aug;22(4):336-46
references.pmid: 25141207
references.citation: Genes Immun. 2010 Sep;11(6):479-89
references.pmid: 20428191
references.citation: J Dent Res. 2011 Oct;90(10):1164-70
references.pmid: 21471325
references.citation: Ann Periodontol. 1996 Nov;1(1):821-78
references.pmid: 9118282
references.citation: J Periodontal Res. 2009 Oct;44(5):598-608
references.pmid: 19076989
references.citation: J Med Microbiol. 2009 Oct;58(Pt 10):1269-74
references.pmid: 19528161
references.citation: Am J Epidemiol. 2009 Feb 15;169(4):505-14
references.pmid: 19126586
references.citation: Cell. 2000 Mar 17;100(6):655-69
references.pmid: 10761931
references.citation: J Exp Med. 2002 Feb 4;195(3):317-26
references.pmid: 11828006
references.citation: J Clin Periodontol. 2005;32 Suppl 6:159-79
references.pmid: 16128836
references.citation: Crit Rev Oral Biol Med. 2003;14(6):430-49
references.pmid: 14656898
references.citation: Nature. 2010 Oct 28;467(7319):1061-73
references.pmid: 20981092
references.citation: Periodontol 2000. 2010 Jun;53:111-23
references.pmid: 20403108
references.citation: J Immunol. 2011 Dec 1;187(11):5615-26
references.pmid: 22048764
references.citation: PLoS One. 2011;6(7):e22526
references.pmid: 21799885
references.citation: Clin Exp Immunol. 2007 Jan;147(1):128-38
references.pmid: 17177972
references.citation: Science. 1988 Apr 22;240(4851):516-8
references.pmid: 3128869
references.citation: J Clin Periodontol. 2012 Apr;39(4):323-32
references.pmid: 22324464
references.citation: J Leukoc Biol. 2008 Dec;84(6):1565-73
references.pmid: 18725394
references.citation: J Dent Res. 2011 May;90(5):632-7
references.pmid: 21245464
references.citation: Front Immunol. 2013 May 16;4:112
references.pmid: 23720660