Abstract
We set out to analyze the role of two major non-HLA gene polymorphisms associated with type 1 diabetes (T1D), PTPN22 1858C/T and insulin gene INS-23 A/T in progression to clinical T1D after the appearance of β-cell autoimmunity. The study population comprised 249 children with HLA-associated T1D susceptibility. All subjects were persistently positive for at least one of the T1D-associated biochemically defined autoantibodies (insulin autoantibody, GAD antibody, or IA-2 antibody), and 136 subjects presented with T1D over a median follow-up of 4.3 years (range 0.0-12.5) after the appearance of the first autoantibody. The PTPN22 1858T allele was strongly associated with progression to T1D after the appearance of the first biochemically defined β-cell autoantibody (hazard ratio 1.68 [95% CI 1.09-2.60], P = 0.02 Cox regression analysis, multivariate test), and the effect remained similar when analyzed after the appearance of the second autoantibody (P = 0.013), whereas INS-23 HphI AA genotype was not associated with progression to clinical diabetes after the appearance of the first or second autoantibody (P = 0.38 and P = 0.88, respectively). The effect of the INS risk genotype seems to be limited to the induction and early phases o...Continue Reading
References
Mar 1, 1997·Nature Genetics·P VafiadisC Polychronakos
Mar 1, 1997·Nature Genetics·A PuglieseD D Patel
Mar 17, 1999·Diabetes·A G ZieglerE Bonifacio
Apr 25, 2001·Diabetologia·A KupilaUNKNOWN Juvenile Diabetes Research Foundation Centre for the Prevention of Type I Diabetes in Finland
Apr 30, 2002·Diabetes·Jinko GrahamUNKNOWN Swedish Childhood Diabetes Study Group
Apr 30, 2002·Hormone Research·Mikael Knip
Apr 16, 2003·Tissue Antigens·B D TaitA Loth
Mar 19, 2004·Immunology·Alberto Pugliese
May 6, 2005·The Journal of Clinical Endocrinology and Metabolism·M KukkoM Knip
Jul 19, 2005·Diabetologia·Robert HermannJ Ilonen
Nov 8, 2005·Nature Genetics·Torkel VangNunzio Bottini
Apr 15, 2006·Diabetologia·R HermannJ Ilonen
May 30, 2006·Seminars in Immunology·Peter K GregersenAnn B Begovich
May 3, 2007·Disease Markers·Antti-Pekka LaineUNKNOWN Finnish Paediatric Diabetes Registry
Jul 10, 2007·The Journal of Clinical Endocrinology and Metabolism·George S Eisenbarth
Sep 20, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Mary RieckJane H Buckner
Feb 7, 2008·Diabetes Care·Antonio PetroneUNKNOWN Immunotherapy Diabetes (IMDIAB) Group
Feb 27, 2008·Journal of Autoimmunity·Johanna AarnisaloRobert Hermann
Jun 17, 2008·Diabetes·Vincent ButtyUNKNOWN DPT-1 Study Group
Feb 4, 2009·Diabetes·Andrea K SteckMarian J Rewers
Apr 17, 2009·The New England Journal of Medicine·Patrick ConcannonGerald T Nepom
Aug 27, 2010·Diabetes·Kati LipponenJorma Ilonen
Mar 25, 2011·BMC Medical Genetics·Lotte B NielsenUNKNOWN Hvidoere Study Group on Childhood Diabetes
Apr 26, 2011·FEBS Letters·Garth L BurnAndrew P Cope
May 11, 2011·BMC Genetics·Robertha A V GarciaRosana P V Brondani
Citations
Aug 17, 2012·Current Diabetes Reports·Johanna Lempainen, Jorma Ilonen
Jan 1, 2012·The Review of Diabetic Studies : RDS·Karen Cerosaletti, Jane H Buckner
Dec 25, 2013·Annual Review of Immunology·Nunzio Bottini, Erik J Peterson
Nov 20, 2013·Acta Diabetologica·Ezio BonifacioAnette-Gabriele Ziegler
Aug 31, 2012·Genes and Immunity·C WinklerA-G Ziegler
Nov 13, 2013·Expert Review of Clinical Immunology·Frans K GorusDaniel G Pipeleers
Nov 26, 2014·Diabetes·Carina TörnUNKNOWN TEDDY Study Group
Oct 30, 2015·Genes and Immunity·M MaziarzUNKNOWN Type 1 Diabetes Genetics Consortium
Jan 31, 2013·Annals of the New York Academy of Sciences·Natalie Nokoff, Marian Rewers
Jun 16, 2015·Journal of Autoimmunity·Johanna LempainenJorma Ilonen
Mar 7, 2014·Diabetes·Yulan JinJin-Xiong She
Jul 12, 2017·Pediatric Diabetes·Brigitte I FrohnertAndrea K Steck
Aug 23, 2017·Genes·Samuel T Jerram, Richard David Leslie
Jul 29, 2017·World Journal of Diabetes·Giuseppe Galvani, Georgia Fousteri
Sep 15, 2017·Diabetes·Jeffrey P KrischerUNKNOWN TEDDY Study Group
Jun 27, 2019·Scientific Reports·Tania SinghIsabella Artner
Sep 1, 2018·Current Diabetes Reports·Laura M JacobsenTodd M Brusko
Jul 25, 2021·International Journal of Molecular Sciences·Witold BauerAdam Krętowski
May 24, 2020·Drug Discovery Today·Labe A Black, Tatiana Zorina