Effect of the PTPN22 and INS risk genotypes on the progression to clinical type 1 diabetes after the initiation of β-cell autoimmunity.

Diabetes
Johanna LempainenJ Ilonen

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

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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 13, 2013·Expert Review of Clinical Immunology·Frans K GorusDaniel G Pipeleers
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
Aug 23, 2017·Genes·Samuel T Jerram, Richard David Leslie
Jul 29, 2017·World Journal of Diabetes·Giuseppe Galvani, Georgia Fousteri
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

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Methods Mentioned

BETA
genotyping

Software Mentioned

SPSS

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