Genome-Wide Association Analysis of Autoantibody Positivity in Type 1 Diabetes Cases

The genetic basis of autoantibody production is largely unknown outside of associations located in the major histocompatibility complex (MHC) human leukocyte antigen (HLA) region. The aim of this study is the discovery of new genetic associations with autoantibody positivity using genome-wide association scan single nucleotide polymorphism (SNP) data in type 1 diabetes (T1D) patients with autoantibody measurements. We measured two anti-islet autoantibodies, glutamate decarboxylase (GADA, n = 2,506), insulinoma-associated antigen 2 (IA-2A, n = 2,498), antibodies to the autoimmune thyroid (Graves') disease (AITD) autoantigen thyroid peroxidase (TPOA, n = 8,300), and antibodies against gastric parietal cells (PCA, n = 4,328) that are associated with autoimmune gastritis. Two loci passed a stringent genome-wide significance level (p<10(-10)): 1q23/FCRL3 with IA-2A and 9q34/ABO with PCA. Eleven of 52 non-MHC T1D loci showed evidence of association with at least one autoantibody at a false discovery rate of 16%: 16p11/IL27-IA-2A, 2q24/IFIH1-IA-2A and PCA, 2q32/STAT4-TPOA, 10p15/IL2RA-GADA, 6q15/BACH2-TPOA, 21q22/UBASH3A-TPOA, 1p13/PTPN22-TPOA, 2q33/CTLA4-TPOA, 4q27/IL2/TPOA, 15q14/RASGRP1/TPOA, and 12q24/SH2B3-GADA and TPOA. Analysis of the TPOA-associated loci in 2,477 cases with Graves' disease identified two new AITD loci (BACH2 and UBASH3A)

Thyroid function, morphology and autoimmunity in children and adolescents with type 1 diabetes mellitus

info:eu-repo/semantics/publishe

Barium and lithium silicate glass ceramics doped with rare earth ions for white LEDs

Novel glasses and glass ceramics with compositions corresponding to stoichiometric lithium and barium dis- ilicates and doped with different combinations of Ce3+, Eu2+,3+, Tb3+, and Dy3+ have been fabricated and studied as prospective light converters for white high-power light emitting diodes and laser diodes. Spatially resolved photoluminescence spectroscopy and structural analysis have been employed. The emission spectra and CIE color coordinates of these materials evidence their good prospective as phosphors for white light sources. Structural analysis proves a high level of crystallization of the ceramics fabricated by annealing the glasses, while spectroscopic study revealed the influence of crystallization on the emission properties of this system. The results show a high potential of these materials be exploited as temperature-resistant phosphors in high-power white light emitting diodes

Systematic Genetic Study of Youth With Diabetes in a Single Country Reveals the Prevalence of Diabetes Subtypes, Novel Candidate Genes, and Response to Precision Therapy.

Identifying gene variants causing monogenic diabetes (MD) increases understanding of disease etiology and allows for implementation of precision therapy to improve metabolic control and quality of life. Here, we aimed to assess the prevalence of MD in youth with diabetes in Lithuania, uncover potential diabetes-related gene variants, and prospectively introduce precision treatment. First, we assessed all pediatric and most young-adult patients with diabetes in Lithuania (n = 1,209) for diabetes-related autoimmune antibodies. We then screened all antibody-negative patients (n = 153) using targeted high-throughput sequencing of &gt;300 potential candidate genes. In this group, 40.7% had MD, with the highest percentage (100%) in infants (diagnosis at ages 0-12 months), followed by those diagnosed at ages &gt;1-18 years (40.3%) and &gt;18-25 years (22.2%). The overall prevalence of MD in youth with diabetes in Lithuania was 3.5% (1.9% for GCK diabetes, 0.7% for HNF1A, 0.2% for HNF4A and ABCC8, 0.3% for KCNJ11, and 0.1% for INS). Furthermore, we identified likely pathogenic variants in 11 additional genes. Microvascular complications were present in 26% of those with MD. Prospective treatment change was successful in &gt;50% of eligible candidates, with C-peptide &gt;252 pmol/L emerging as the best prognostic factor

The course of diabetes in children, adolescents and young adults: does the autoimmunity status matter?

Initial classification of diabetes of young may require revision to improve diagnostic accuracy of different forms of diabetes. The aim of our study was to examine markers of beta-cell autoimmunity in a cohort of young (0-25 years) patients with type 1 diabetes and compare the presentation and course of the disease according to the presence of pancreatic antibodies