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.

Keywords::

• Latent autoimmune diabetes in adult
• LADA
• Type 1 diabetes
• ZnT8A
• young-onset type 1 diabetes
• adult-onset type 1 diabetes
• autoimmunity
• rs13266634

Acknowledgements

The HUNT study was performed as a collaboration between the HUNT Research Centre (Faculty of Medicine, Norwegian University of Science and Technology (NTNU)), Nord-Trøndelag County Council, Central Norway Health Authority, and the Norwegian Institute of Public Health.

Declaration of interest : Our study was funded by the liaison committee of the Central Norway Regional Health Authority and the NTNU, and the liaison committee of St. Olav's Hospital Trust and the Faculty of Medicine, NTNU. The authors declare that there are no conflicts of interest. The authors are responsible for the content and writing of this paper.