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Leif Groop

Leif Groop

Principal investigator

Leif Groop

Zinc Transporter 8 Autoantibodies and Their Association With SLC30A8 and HLA-DQ Genes Differ Between Immigrant and Swedish Patients With Newly Diagnosed Type 1 Diabetes in the Better Diabetes Diagnosis Study.

Author

  • Ahmed Delli
  • Fariba Vaziri Sani
  • Bengt Lindblad
  • Helena Larsson
  • Annelie Carlsson
  • Gun Forsander
  • Sten Ivarsson
  • Johnny Ludvigsson
  • Ingrid Kockum
  • Claude Marcus
  • Ulf Samuelsson
  • Eva Ortqvist
  • Leif Groop
  • George P Bondinas
  • George K Papadopoulos
  • Åke Lernmark

Summary, in English

We examined whether zinc transporter-8 autoantibodies (ZnT8A; arginine ZnT8-RA, tryptophan ZnT8-WA, and glutamine ZnT8-QA variants) differed between immigrant and Swedish patients due to different polymorphisms of SLC30A8, HLA-DQ, or both. Newly diagnosed autoimmune (≥1 islet autoantibody) T1D type 1 diabetic patients (n = 2,964, <18 years, 55% male) were ascertained in the Better Diabetes Diagnosis study. Two subgroups were identified: Swedes (n = 2,160, 73%) and immigrants (non-Swedes; n = 212, 7%). Non-Swedes had less frequent ZnT8-WA (38%) than Swedes (50%), consistent with a lower frequency in the non-Swedes (37%) of SLC30A8 CT+TT (RW+WW) genotypes than in the Swedes (54%). ZnT8-RA (57 and 58%, respectively) did not differ despite a higher frequency of CC (RR) genotypes in non-Swedes (63%) than Swedes (46%). We tested whether this inconsistency was due to HLA-DQ as 2/X (2/2; 2/y; y is anything but 2 or 8), which was a major genotype in non-Swedes (40%) compared with Swedes (14%). In the non-Swedes only, 2/X (2/2; 2/y) was negatively associated with ZnT8-WA and ZnT8-QA but not ZnT8-RA. Molecular simulation showed nonbinding of the relevant ZnT8-R peptide to DQ2, explaining in part a possible lack of tolerance to ZnT8-R. At diagnosis in non-Swedes, the presence of ZnT8-RA rather than ZnT8-WA was likely due to effects of HLA-DQ2 and the SLC30A8 CC(RR) genotypes.

Department/s

  • Celiac Disease and Diabetes Unit
  • Paediatrics (Lund)
  • Vascular Diseases - Clinical Research
  • Paediatric Endocrinology
  • Genomics, Diabetes and Endocrinology
  • EXODIAB: Excellence of Diabetes Research in Sweden

Publishing year

2012

Language

English

Pages

2556-2564

Publication/Series

Diabetes

Volume

61

Issue

10

Document type

Journal article

Publisher

American Diabetes Association Inc.

Topic

  • Endocrinology and Diabetes

Status

Published

Research group

  • Diabetes and Celiac Unit
  • Vascular Diseases - Clinical Research
  • Paediatric Endocrinology
  • Genomics, Diabetes and Endocrinology

ISBN/ISSN/Other

  • ISSN: 1939-327X