Prevalence of ZnT8 antibody in relation to phenotype and SLC30A8 polymorphism in adult autoimmune diabetes. Results from the HUNT study, Norway

Abstract

Zinc transporter 8 (ZnT8), a product of the SLC30A8 gene, is a target-antigen in autoimmune diabetes. Associations between ZnT8 antibody (ZnT8A), phenotype and the genetic variant rs13266634 in the SLC30A8 gene have primarily been studied in patients with young-onset diabetes. We explored such associations in adult-onset autoimmune diabetes identified from the all-population based Nord-Trøndelag health Study (HUNT) ZnT8A (assayed by a fusion probe of C-terminal Arg325 and Trp325), and antibodies against glutamic decarboxylase (GADA) and tyrosine phosphatase-like protein insulinoma antigen-2 (IA-2A) were analysed in 266 subjects classified as having adult-onset autoimmune diabetes ( ≥ 25 years of age at diagnosis). Of these, 161 subjects fulfilled the criteria of latent autoimmune diabetes in adults (LADA), whereas 105 subjects were termed “classical” type 1 diabetes. Ten out of 161 LADA (6.2%) and 23 out of 105 adult-onset “classical” type 1 diabetic patients (22%) were ZnT8A positive. Adult-onset diabetic subjects positive both for GADA and IA-2A (n = 17), had lower waist circumference (p = 0.024) and higher fasting glucose levels (p = 0.023) than those positive both for GADA and ZnT8A (n = 13). Genotyping results of rs13266634 (available in 178 adult-onset diabetic subjects), showed a tendency for association between ZnT8A positivity and the TT- and CC genotypes of SNP rs13266634 (p = 0.101) using the standard cut-off level of 0.06ai, and a significant association at a lower cut-off level of 0.01ai (p = 0.005). We conclude that ZnT8A positivity in a population of adult-onset autoimmune diabetes is a less strong marker of autoimmunity than IA-2A. Further, positivity could be influenced by polymorphism of the SLC30A8 gene.