Abstract
There is a scarcity of data of zinc transporter-8 autoantibody (ZnT8A) on mixed populations such as Brazilian. Therefore, we evaluated the relevance of ZnT8A for type 1 diabetes (T1D) diagnosis and the role of ZnT8 coding gene (SLC30A8) in T1D predisposition. Patients with T1D (n = 629; diabetes duration = 11 (6–16) years) and 651 controls were genotyped for SLC30A8 rs16889462 and rs2466295 variants (BeadXpress platform). ZnT8 triple antibody was measured by ELISA; glutamic acid decarboxylase (GAD65A) and protein tyrosine phosphatase (IA-2A) autoantibodies by radioimmunoassay. Results: Znt8A was detected in 68.7% of recent-onset T1D patients and 48.9% of the entire patient cohort, similar to GAD65A (68.3% and 47.2%) and IA-2A (64.8% and 42.4%) positivities respectively. ZnT8A was the only antibody in 8.4% of patients. Znt8A and IA2A frequencies and titers were independent of gender and ethnicity, whereas GAD65A titers were greater in females. The diabetes duration-dependent decline in ZnT8A frequency was similar to GAD65A and IA-2A. The SLC30A8 rs2466293 AG + GG genotypes were associated with T1D risk in non-European descents (56.2% × 42.9%; p = 0.018), and the GG genotype with higher ZnT8A titers in recent-onset T1D: 834.5 IU/mL (711.3–2190.0) × 281 IU/mL (10.7–726.8); p = 0.027. Conclusion ZnT8A detection increases T1D diagnosis rate even in mixed populations. SLC30A8 rs2466293 was associated with T1D predisposition in non-European descents.
Highlights
Autoantibodies to ZnT8 (ZnT8A) complement the established set of type 1 diabetes-associated autoantibodies to insulin (IAA), glutamic acid decarboxylase (GAD65A), and protein tyrosine phosphatase, which are important for predicting and confirming the T1D diagnosis[5]
As data on autoimmune manifestations in the Brazilian population are scarce, the aim of our study was to estimate the prevalence of zinc transporter-8 autoantibody (ZnT8A) in T1D patients and determine the utility of ZnT8A as a T1D immunity marker, either alone in GAD65A- and IA-2A-negative subjects or in conjunction with them
ZnT8A was the only autoantibody observed in six control subjects (1.9%, 3F:3M) aged 1.9 to 27 years, who tested negative for GAD65A and IA-2A, and its frequency did not differ from that of GAD65A (1.7%) or IA2-A (1.7%) in the controls (p > 0.05)
Summary
Autoantibodies to ZnT8 (ZnT8A) complement the established set of type 1 diabetes-associated autoantibodies to insulin (IAA), glutamic acid decarboxylase (GAD65A), and protein tyrosine phosphatase (insulinoma-2 antigen antibody, IA-2A), which are important for predicting and confirming the T1D diagnosis[5]. Amino acid changes at position 325 of ZnT8 coding gene SLC30A8, which are represented by arginine (ZnT8-R), tryptophan (ZnT8-W) and glutamine (ZnT8-Q), are determined by the rs13266634 and rs16889462 missense mutations[6, 7], which represent three antigenic epitopes. Both SNPs are in linkage disequilibrium[14] and together with rs2466295 seem to be related to the T2D risk and response to therapy[14,15,16]. We evaluated the roles of SLC30A8 rs16889462 and rs2466295 in T1D pathogenesis
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