Relationship between ZnT8Ab, the SLC30A8 gene and disease progression in children with newly diagnosed type 1 diabetes

Autoimmunity. 2011 Dec;44(8):616-23. doi: 10.3109/08916934.2011.576724. Epub 2011 May 23.

Abstract

Autoantibodies against the newly established autoantigen in type 1 diabetes, zinc transporter 8, ZnT8, are presented as two types, ZnT8RAb and ZnT8WAb. The rs13266634 variant of the SLC30A8 gene has recently been found to determine the type of ZnT8Ab. The aim of this study was to explore the impact of this genetic variant and the ZnT8Ab on the residual beta-cell function during disease progression the first year after disease diagnosis in children with newly diagnosed type 1 diabetes. This cohort consists of 257 children aged < 16 years, all patients were newly diagnosed with type 1 diabetes. A Boost-test was carried out at 1, 6, and 12 months to characterize the residual beta-cell function. Carriers of the CC and CT genotype groups of the rs13266634 SNP of the SLC30A8 gene had higher stimulated C-peptide levels the first year after onset compared with those of the TT genotype group (29%, p = 0.034). CC genotype carriers were highly associated with the presence of ZnT8RAb subtype during disease progression (compared with TT, p < 0.0001). On the other hand, the TT genotype was associated with the presence of ZnT8WAb subtype during disease progression (compared with CC, p < 0.0001). The C allele of the SLC30A8 gene is associated with preserved beta-cell function in type 1 diabetes patients. The genetic determination of the rs13266634 variant on the ZnT8Ab specificity is sustained the first 12 months after the diagnosis of type 1 diabetes in a pediatric cohort.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age of Onset
  • Alleles
  • Antibody Specificity
  • Autoantibodies / immunology*
  • Cation Transport Proteins / genetics*
  • Cation Transport Proteins / immunology*
  • Child
  • Child, Preschool
  • Diabetes Mellitus, Type 1 / epidemiology
  • Diabetes Mellitus, Type 1 / genetics*
  • Diabetes Mellitus, Type 1 / immunology*
  • Disease Progression*
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • HLA Antigens / genetics
  • HLA Antigens / immunology
  • Humans
  • Insulin-Secreting Cells / metabolism
  • Male
  • Polymorphism, Single Nucleotide
  • Zinc Transporter 8

Substances

  • Autoantibodies
  • Cation Transport Proteins
  • HLA Antigens
  • SLC30A8 protein, human
  • Zinc Transporter 8