The prevalence and predictive value of the SLC30A8 R325W polymorphism and zinc transporter 8 autoantibodies in the development of GDM and postpartum type 1 diabetes

Endocrine. 2016 Sep;53(3):740-6. doi: 10.1007/s12020-016-0932-7. Epub 2016 Mar 22.

Abstract

The objectives were to evaluate possible associations between the SLC30A8 R325W polymorphism and gestational diabetes mellitus (GDM) as well as postpartum development of type 2 diabetes. Furthermore, we wanted to confirm the prevalence of zinc transporter 8 autoantibodies (ZnT8A), as previously reported, in a larger population and study its predictive value in relation to other β cell specific autoantibodies in postpartum development of type 1 diabetes. Women diagnosed with GDM (n = 776) and women without diabetes (n = 511) were included in the study. Autoantibodies were analyzed in all women using enzyme-linked immunosorbent assay. DNA was extracted when possible from women with GDM (n = 536) and all of the controls. R325W was detected through polymerase chain reaction and specific restriction digestion. The R325W C-allele were more frequent in women with GDM compared to in controls (OR 1.47, 95 % CI 1.16-1.88, p = 0.0018) but not significantly increased in women with GDM and postpartum development of type 2 diabetes. Autoantibodies were found in 6.8 % (53/776) of the women with GDM and approximately 3.2 % (25/776) were ZnT8A positive. Approximately 19 % (10/53) of the autoantibody positive women with GDM developed postpartum type 1 diabetes. In conclusion, this is the first study to report a significant association between the R325W C-allele and increased risk of developing GDM. All of the autoantibody positive women with GDM who developed postpartum type 1 diabetes were positive for autoantibodies against glutamic acid decarboxylase (GADA). Thus ZnT8A did not have any additional predictive value in postpartum development of type 1 diabetes.

Keywords: Autoantibodies; Gestational diabetes mellitus; Prediction of type 1 diabetes; SNP.

MeSH terms

  • Adult
  • Alleles
  • Autoantibodies / blood*
  • Cation Transport Proteins / genetics*
  • Cation Transport Proteins / immunology*
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / etiology*
  • Diabetes Mellitus, Type 1 / genetics
  • Diabetes Mellitus, Type 1 / immunology
  • Diabetes, Gestational / blood
  • Diabetes, Gestational / etiology*
  • Diabetes, Gestational / genetics
  • Diabetes, Gestational / immunology
  • Female
  • Gene Frequency
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Genotype
  • Glutamate Decarboxylase / immunology
  • Humans
  • Polymorphism, Single Nucleotide*
  • Postpartum Period
  • Pregnancy
  • Zinc Transporter 8

Substances

  • Autoantibodies
  • Cation Transport Proteins
  • SLC30A8 protein, human
  • Zinc Transporter 8
  • Glutamate Decarboxylase