title: 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.
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.
authors.affiliation: Department of Clinical Sciences, Diabetes Research Laboratory, Lund University, B11, BMC, 221 84, Lund, Sweden. jonatan.dereke@med.lu.se.
authors.forename: Jonatan
authors.identifier: http://orcid.org/0000-0002-5653-8614
authors.initials: J
authors.lastname: Dereke
authors.affiliation: Department of Clinical Sciences, Diabetes Research Laboratory, Lund University, B11, BMC, 221 84, Lund, Sweden.
authors.forename: Sanna
authors.initials: S
authors.lastname: Palmqvist
authors.affiliation: Department of Clinical Sciences, Diabetes Research Laboratory, Lund University, B11, BMC, 221 84, Lund, Sweden.|Department of Pediatrics, Helsingborg Hospital, Helsingborg, Sweden.
authors.forename: Charlotta
authors.initials: C
authors.lastname: Nilsson
authors.affiliation: Department of Clinical Sciences, Diabetes Research Laboratory, Lund University, B11, BMC, 221 84, Lund, Sweden.|Department of Endocrinology, Skåne University Hospital, Lund, Sweden.
authors.forename: Mona
authors.initials: M
authors.lastname: Landin-Olsson
authors.affiliation: Department of Clinical Sciences, Diabetes Research Laboratory, Lund University, B11, BMC, 221 84, Lund, Sweden.
authors.forename: Magnus
authors.initials: M
authors.lastname: Hillman
mesh_terms: D000328:Adult; D000483:Alleles; D001323:Autoantibodies / Q000097:blood*; D027682:Cation Transport Proteins / Q000235:genetics* / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D016640:Diabetes, Gestational / Q000097:blood / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005968:Glutamate Decarboxylase / Q000276:immunology; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D049590:Postpartum Period; D011247:Pregnancy; D000075703:Zinc Transporter 8
chemical_list: D001323:Autoantibodies; D027682:Cation Transport Proteins; C492522:SLC30A8 protein, human; D000075703:Zinc Transporter 8; D005968:Glutamate Decarboxylase
keywords: Autoantibodies; Gestational diabetes mellitus; Prediction of type 1 diabetes; SNP