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The Influence of Type 1 Diabetes Genetic Susceptibility Regions, Age, Sex, and Family History to the Progression from Multiple Autoantibodies to Type 1 Diabetes:A TEDDY Study Report : A TEDDY Study Report

Author:
  • Jeffrey P. Krischer
  • Xiang Liu
  • Åke Lernmark
  • William A. Hagopian
  • Marian J. Rewers
  • Jin-Xiong She
  • Jorma Toppari
  • Anette-G Ziegler
  • Beena Akolkar
Publishing year: 2017-09-13
Language: English
Pages: 3122-3129
Publication/Series: Diabetes
Volume: 66
Issue: 12
Document type: Journal article
Publisher: American Diabetes Association Inc.

Abstract english

This paper seeks to determine whether factors related to autoimmunity risk remain significant after the initiation of two or more diabetes-related autoantibodies and continue to contribute to T1D risk among autoantibody positive children in The Environmental Determinants of Diabetes in the Young (TEDDY) study. Characteristics included are age at multiple autoantibody positivity, sex, selected high-risk HLA-DR-DQ genotypes, relationship to a family member with T1D, autoantibody at seroconversion, INS gene (rs1004446_A), and non-HLA gene polymorphisms identified by the Type 1 Diabetes Genetics Consortium. The risk of progression to T1D was not different among those with or without a family history of T1D (p=0.39) nor HLA-DR-DQ genotypes (p=0.74). Age at developing multiple autoantibodies (HR=0.96 per 1 month increase in age, 95% CI=0.95, 0.97, p<0.001) and the type of first autoantibody (when more than a single autoantibody was the first appearing indication of seroconversion [p=0.006]) were statistically significant. Female sex was also a significant risk factor (p=0.03). Three SNPs were associated with increased diabetes risk (rs10517086_A, [p=0.03], rs1534422_G, [p=0.006], and rs2327832_G in TNFAIP3 [p=0.03]), and one with decreased risk (rs1004446_A in INS, [p=0.006]). The TEDDY data suggest that non-HLA gene polymorphisms may play a different role in the initiation of autoimmunity than they do in progression to T1D once autoimmunity has appeared. The strength of these associations may be related to the age of the population and the high-risk HLA-DR-DQ subtypes studied.

Keywords

  • Endocrinology and Diabetes
  • Journal Article

Other

Published
  • Diabetes and Celiac Unit
  • ISSN: 1939-327X
E-mail: ake [dot] lernmark [at] med [dot] lu [dot] se

Principal investigator

Diabetes and Celiac Unit

+46 40 39 19 01

+46 70 616 47 79

60:11:015

Jan Waldenströms gata 35, Malmö

33

Lund University Diabetes Centre, CRC, SUS Malmö, Jan Waldenströms gata 35, House 91:12. SE-214 28 Malmö. Telephone: +46 40 39 10 00