Autoantibodies to Zinc Transporter 8 and SLC30A8 Genotype in Type 1 Diabetes Childhood: A Pioneering Study in North Africa

Abstract

Background. Type 1 diabetes (T1D) occurs as a result of insulin deficiency due to destructive lesions of pancreatic β cells. In addition to classical autoantibodies (Abs) to islet cell antigens, antizinc transporter 8 Abs (ZnT8-Ab) have been recently described in T1D. Objective. As no data on ZnT8-Ab in Tunisian patients has been reported, we aim to evaluate the relationships between ZnT8-Ab, ZnT8 coding gene (SLC30A8) promoter polymorphism, and T1D risk in newly diagnosed children. Methods. ZnT8-Ab were measured in the serum of T1D newly affected children (n=156) who were admitted to the pediatric department of the Hedi Chaker University Hospital of Sfax. Rs13266634 was genotyped in T1D children and 79 of their first-degree parents. The SPSS software was used to analyze the serological data. Allelic association analysis was conducted with family-based association tests implemented in the FBAT program v1.5.1. Results. ZnT8-Ab was detected in 66/156 (42.3%) of T1D newly diagnosed children. Among them, 6 (9%) presented ZnT8-Ab as the only humoral marker. The inclusion of ZnT8-Ab increased the number of Ab-positive patients to 90% and reduced the negative ones by 27%. There was no evidence of any overtransmission of any allele of the rs13266634 C/T polymorphism from parents to affected T1D children, nor of any correlation with any clinical or serological parameter. After the T1D disease onset age adjustment, a significant association was observed with the C allele suggesting that it could have a susceptibility role. Conclusion. ZnT8-Ab appears as a relevant diagnostic marker for T1D in Tunisian children, especially at the onset of the disease as teenagers.