title: Zinc transporter type 8 autoantibodies (ZnT8A): prevalence and phenotypic associations in latent autoimmune diabetes patients and patients with adult onset type 1 diabetes.
abstract: OBJECTIVE
  Patients with type 1 diabetes have antibodies to ZnT8 protein is encoded by SLC30A8. The C-allele of the R325 W variant in SLC30A8 is associated with type 2 diabetes and reduced beta-cell function in non-diabetic subjects. Our aim was to assess the prevalence of ZnT8 autoantibodies (ZnT8A) in patients with adult-onset diabetes, and to characterize associations between ZnT8A and phenotype, as well as SLC30A8 and HLA-DQB1 genotypes.
  
  
  METHODS
  ZnT8A were analyzed in patients diagnosed with diabetes >35 years (type 1 diabetes: n = 274; Latent autoimmune diabetes in adults (LADA): n = 294). SLC30A8 R325 W (rs13266634) and HLA-DQB1 alleles were genotyped in all patients and 537 non-diabetic control subjects.
  
  
  RESULTS
  ZnT8A were significantly more prevalent in LADA (34.3%) compared to adult-onset type 1 diabetes (18.7%, p < 0.0001). Among the patients with adult-onset type 1 diabetes, ZnT8A were associated with shorter disease duration [4.4 (6.0) vs. 10.8 (11.2) years, p < 0.0001], whereas no such association was observed among patients with LADA. The SLC30A8 R325 W variant was associated with LADA with low GADA levels [SLC30A8 CC: OR (95% CI): 1.46 (1.00 - 2.13), p = 0.049], and reduced insulin secretion among the non-diabetic subjects and the patients with LADA.
  
  
  CONCLUSIONS
  ZnT8A were more common and more persistent in patients with LADA compared to adult-onset type 1 diabetes, but their presence was not associated with specific phenotypic characteristics. The SLC30A8 CC genotype adds to the genetic heterogeneity of LADA linked to GADA reactivity.
authors.affiliation: Research Program for Molecular Medicine, Helsinki University and Department of Medicine, Helsinki University Hospital, Helsinki, Finland.
authors.forename: Mette K
authors.initials: MK
authors.lastname: Andersen
authors.forename: Taina
authors.initials: T
authors.lastname: Härkönen
authors.forename: Carol
authors.initials: C
authors.lastname: Forsblom
authors.forename: Per-Henrik
authors.initials: PH
authors.lastname: Groop
authors.forename: Mikael
authors.initials: M
authors.lastname: Knip
authors.forename: Tiinamaija
authors.initials: T
authors.lastname: Tuomi
mesh_terms: D000328:Adult; D000367:Age Factors; D017668:Age of Onset; D000368:Aged; D001323:Autoantibodies / Q000276:immunology*; D027682:Cation Transport Proteins / Q000235:genetics / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology*; D005260:Female; D005838:Genotype; D059866:HLA-DQ beta-Chains / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D015995:Prevalence; D000075703:Zinc Transporter 8
chemical_list: D001323:Autoantibodies; D027682:Cation Transport Proteins; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; C492522:SLC30A8 protein, human; D000075703:Zinc Transporter 8