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.

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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; Vaziri Sani, Fariba; Lindblad, Bengt; Larsson, Helena; Carlsson, Annelie; Forsander, Gun; Ivarsson, Sten; Ludvigsson, Johnny; Kockum, Ingrid; Marcus, Claude; Samuelsson, Ulf; Ortqvist, Eva; Groop, Leif; Bondinas, George P; Papadopoulos, George K; Lernmark, Åke.

In: Diabetes, Vol. 61, No. 10, 2012, p. 2556-2564.

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Delli, Ahmed ; Vaziri Sani, Fariba ; Lindblad, Bengt ; Larsson, Helena ; Carlsson, Annelie ; Forsander, Gun ; Ivarsson, Sten ; Ludvigsson, Johnny ; Kockum, Ingrid ; Marcus, Claude ; Samuelsson, Ulf ; Ortqvist, 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. In: Diabetes. 2012 ; Vol. 61, No. 10. pp. 2556-2564.

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TY - JOUR

T1 - 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.

AU - Delli, Ahmed

AU - Vaziri Sani, Fariba

AU - Lindblad, Bengt

AU - Larsson, Helena

AU - Carlsson, Annelie

AU - Forsander, Gun

AU - Ivarsson, Sten

AU - Ludvigsson, Johnny

AU - Kockum, Ingrid

AU - Marcus, Claude

AU - Samuelsson, Ulf

AU - Ortqvist, Eva

AU - Groop, Leif

AU - Bondinas, George P

AU - Papadopoulos, George K

AU - Lernmark, Åke

PY - 2012

Y1 - 2012

N2 - 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.

AB - 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.

U2 - 10.2337/db11-1659

DO - 10.2337/db11-1659

M3 - Article

C2 - 22787139

VL - 61

SP - 2556

EP - 2564

JO - Diabetes

JF - Diabetes

SN - 1939-327X

IS - 10

ER -