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 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.
Department of Clinical Sciences, Diabetes and Celiac Diseases, Lund University, Malmö, Sweden. ahmed.delli@med.lu.se
Ahmed J
AJ
Delli
Fariba
F
Vaziri-Sani
Bengt
B
Lindblad
Helena
H
Elding-Larsson
Annelie
A
Carlsson
Gun
G
Forsander
Sten A
SA
Ivarsson
Johnny
J
Ludvigsson
Ingrid
I
Kockum
Claude
C
Marcus
Ulf
U
Samuelsson
Eva
E
Örtqvist
Leif
L
Groop
George P
GP
Bondinas
George K
GK
Papadopoulos
Åke
Å
Lernmark
D000293:Adolescent; D001323:Autoantibodies / Q000235:genetics / Q000276:immunology*; D044383:Black People / Q000235:genetics; D027682:Cation Transport Proteins / Q000235:genetics* / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology; D005260:Female; D006683:HLA-DQ Antigens / Q000235:genetics*; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D013548:Sweden; D044465:White People / Q000235:genetics*; D000075703:Zinc Transporter 8
D001323:Autoantibodies; D027682:Cation Transport Proteins; D006683:HLA-DQ Antigens; C492522:SLC30A8 protein, human; D000075703:Zinc Transporter 8