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
2012 (English)In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 61, no 10, 2556-2564 p.Article in journal (Refereed) Published
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 (andgt;= 1 islet autoantibody) type 1 diabetic patients (n = 2,964, andlt;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.
Place, publisher, year, edition, pages
American Diabetes Association , 2012. Vol. 61, no 10, 2556-2564 p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-84883DOI: 10.2337/db11-1659ISI: 000309304600020OAI: oai:DiVA.org:liu-84883DiVA: diva2:564019
Funding Agencies|Swedish Child Diabetes Foundation (Barndiabetesfonden)||National Institutes of Health|DK-63861DK-26190|Swedish Research Council||KA Wallenberg Foundation||European Union|202013|Swedish Diabetes Association||Skane County Council Foundation for Research and Development||Swedish Association of Local Authorities and Regions||EU funds||Hellenic State funds||2012-11-012012-10-262014-10-29