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.

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.

• 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
• Department/s: Celiac Disease and Diabetes Unit; Paediatrics (Lund); Vascular Diseases - Clinical Research; Paediatric Endocrinology; Translational Muscle Research; EXODIAB: Excellence of Diabetes Research in Sweden
• Publishing year: 2012
• Language: English
• Pages: 2556-2564
• Publication/Series: Diabetes
• Volume: 61
• Issue: 10
• Full text: - 1 MB; Download statistics
• Links: http://www.ncbi.nlm.nih.gov/pubmed/22787139?dopt=Abstract; http://dx.doi.org/10.2337/db11-1659
• Document type: Journal article
• Publisher: American Diabetes Association Inc.
• Topic: Endocrinology and Diabetes
• Status: Published
• Research group: Celiac Disease and Diabetes Unit; Vascular Diseases - Clinical Research; Paediatric Endocrinology; Genomics, Diabetes and Endocrinology
• ISBN/ISSN/Other: ISSN: 1939-327X