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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 LU ; Vaziri Sani, Fariba LU ; Lindblad, Bengt LU ; Larsson, Helena LU ; Carlsson, Annelie LU ; Forsander, Gun; Ivarsson, Sten LU ; Ludvigsson, Johnny; Kockum, Ingrid and Marcus, Claude, et al. (2012) In Diabetes 61(10). p.2556-2564
Abstract
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... (More)
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. (Less)
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type
Contribution to journal
publication status
published
subject
in
Diabetes
volume
61
issue
10
pages
2556 - 2564
publisher
American Diabetes Association Inc.
external identifiers
  • wos:000309304600020
  • pmid:22787139
  • scopus:84866596750
ISSN
1939-327X
DOI
10.2337/db11-1659
language
English
LU publication?
yes
id
9fa87c2d-ed90-43fc-823b-85b056528f4c (old id 2967220)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22787139?dopt=Abstract
date added to LUP
2012-08-09 19:09:13
date last changed
2017-11-12 03:45:09
@article{9fa87c2d-ed90-43fc-823b-85b056528f4c,
  abstract     = {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, &lt;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       = {Delli, Ahmed and Vaziri Sani, Fariba and Lindblad, Bengt and Larsson, Helena and Carlsson, Annelie and Forsander, Gun and Ivarsson, Sten and Ludvigsson, Johnny and Kockum, Ingrid and Marcus, Claude and Samuelsson, Ulf and Ortqvist, Eva and Groop, Leif and Bondinas, George P and Papadopoulos, George K and Lernmark, Åke},
  issn         = {1939-327X},
  language     = {eng},
  number       = {10},
  pages        = {2556--2564},
  publisher    = {American Diabetes Association Inc.},
  series       = {Diabetes},
  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.},
  url          = {http://dx.doi.org/10.2337/db11-1659},
  volume       = {61},
  year         = {2012},
}