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 [Elektronisk resurs]
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Delli, Ahmed J (författare)
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Vaziri-Sani, Fariba (författare)
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Lindblad, Bengt (författare)
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Elding-Larsson, Helena (författare)
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Carlsson, Annelle (författare)
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Forsander, Gun (författare)
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Ivarsson, Sten A (författare)
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Ludvigsson, Johnny (författare)
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Kockum, Ingrid (författare)
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Marcus, Claude (författare)
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Samuelsson, Ulf (författare)
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Ortqvist, Eva (författare)
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Groop, Leif (författare)
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P Bondinas, George (författare)
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Papadopoulos, George K (författare)
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Lernmark, Ake (författare)
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- Linköpings universitet Institutionen för klinisk och experimentell medicin (utgivare)
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Alternativt namn: IKE
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Alternativt namn: Linköping University. Department of Clinical and Experimental Medicine
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Alternativt namn: Linköping University. Faculty of Health Sciences. Department of Clinical and Experimental Medicine
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Linköpings universitet Hälsouniversitetet (utgivare)
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Östergötlands Läns Landsting Barn- och kvinnocentrum (utgivare)
- American Diabetes Association 2012
- Engelska.
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Ingår i: Diabetes. - 0012-1797. ; 61:10, 2556-2564
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- 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.
Ämnesord
- Medical and Health Sciences (hsv)
- Medicin och hälsovetenskap (hsv)
- MEDICINE (svep)
- MEDICIN (svep)
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