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

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

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) type 1 di...

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Main Authors: Delli, Ahmed J., Vaziri-Sani, Fariba, Lindblad, Bengt, Elding-Larsson, Helena, Carlsson, Annelie, Forsander, Gun, Ivarsson, Sten A., Ludvigsson, Johnny, Kockum, Ingrid, Marcus, Claude, Samuelsson, Ulf, Örtqvist, Eva, Groop, Leif, Bondinas, George P., Papadopoulos, George K., Lernmark, Åke
Format: Online
Language:English
Published: American Diabetes Association 2012
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3447907/
id pubmed-3447907
recordtype oai_dc
spelling pubmed-34479072013-10-01 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 Delli, Ahmed J. Vaziri-Sani, Fariba Lindblad, Bengt Elding-Larsson, Helena Carlsson, Annelie Forsander, Gun Ivarsson, Sten A. Ludvigsson, Johnny Kockum, Ingrid Marcus, Claude Samuelsson, Ulf Örtqvist, Eva Groop, Leif Bondinas, George P. Papadopoulos, George K. Lernmark, Åke Immunology and Transplantation 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) 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. American Diabetes Association 2012-10 2012-09-13 /pmc/articles/PMC3447907/ /pubmed/22787139 http://dx.doi.org/10.2337/db11-1659 Text en © 2012 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Delli, Ahmed J.
Vaziri-Sani, Fariba
Lindblad, Bengt
Elding-Larsson, Helena
Carlsson, Annelie
Forsander, Gun
Ivarsson, Sten A.
Ludvigsson, Johnny
Kockum, Ingrid
Marcus, Claude
Samuelsson, Ulf
Örtqvist, Eva
Groop, Leif
Bondinas, George P.
Papadopoulos, George K.
Lernmark, Åke
spellingShingle Delli, Ahmed J.
Vaziri-Sani, Fariba
Lindblad, Bengt
Elding-Larsson, Helena
Carlsson, Annelie
Forsander, Gun
Ivarsson, Sten A.
Ludvigsson, Johnny
Kockum, Ingrid
Marcus, Claude
Samuelsson, Ulf
Örtqvist, Eva
Groop, Leif
Bondinas, George P.
Papadopoulos, George K.
Lernmark, Åke
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_facet Delli, Ahmed J.
Vaziri-Sani, Fariba
Lindblad, Bengt
Elding-Larsson, Helena
Carlsson, Annelie
Forsander, Gun
Ivarsson, Sten A.
Ludvigsson, Johnny
Kockum, Ingrid
Marcus, Claude
Samuelsson, Ulf
Örtqvist, Eva
Groop, Leif
Bondinas, George P.
Papadopoulos, George K.
Lernmark, Åke
author_sort Delli, Ahmed J.
title 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
title_short 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_sort 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
description 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) 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.
publisher American Diabetes Association
publishDate 2012
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3447907/
_version_ 1611910718507974656

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