PDE12 in type 1 diabetes

• Published in: Scientific reports Vol. 12; no. 1; p. 18149
• Main Authors: Tekin, Hasim, Josefsen, Knud, Krogvold, Lars, Dahl-Jørgensen, Knut, Gerling, Ivan, Pociot, Flemming, Buschard, Karsten
• Format: Journal Article
• Language: English; Norwegian
• Published: London Nature Publishing Group UK 28.10.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 692/308; 692/420; 692/699/255/2514; 692/699/2743/137; 692/699/2743/137/1418; Adolescent; Child; Coronaviruses; COVID-19; COVID-19 - genetics; Diabetes; Diabetes mellitus (insulin dependent); Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 1 - genetics; Diabetes Mellitus, Type 1 - metabolism; Diabetes Mellitus, Type 2 - genetics; Humanities and Social Sciences; Humans; Interferon-alpha; multidisciplinary; RNA; Science; Science (multidisciplinary); Single-nucleotide polymorphism; α-Interferon
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-022-22890-x

Type 1 diabetes (T1D) incidence is increased after COVID-19 infection in children under 18 years of age. Interferon-α-activated oligoadenylate synthetase and downstream RNAseL activation degrade pathogen RNA, but can also damage host RNA when RNAseL activity is poorly regulated. One such regulator is PDE12 which degrades 2′-5′ oligoadenylate units, thereby decreasing RNAseL activity. We analyzed PDE12 expression in islets from non-diabetic donors, individuals with newly (median disease duration 35 days) and recently (5 years) diagnosed T1D, and individuals with type 2 diabetes (T2D). We also analyzed PDE12 single-nucleotide polymorphisms (SNPs) relative to T1D incidence. PDE12 expression was decreased in individuals with recently diagnosed T1D, in three of five individuals with newly diagnosed T1D, but not in individuals with T2D. Two rare PDE12 SNPs were found to have odds ratios of 1.80 and 1.74 for T1D development. We discuss whether decreased PDE12 expression after COVID-19 infection might be part of the up to 2.5-fold increase in T1D incidence.