Genetic Variants Associated with Neuropeptide Y Autoantibody Levels in Newly Diagnosed Individuals with Type 1 Diabetes
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(1) Autoantibodies to the leucine variant of neuropeptide Y (NPY-LA) have been found in individuals with type 1 diabetes (T1D). We investigated the association between the levels of NPY-LA and single nucleotide polymorphisms (SNP) to better understand the genetic regulatory mechanisms of autoimmunity in T1D and the functional impacts of increased NPY-LA levels. (2) NPY-LA measurements from serum and SNP genotyping were done on 560 newly diagnosed individuals with T1D. SNP imputation with the 1000 Genomes reference panel was followed by an association analysis between the SNPs and measured NPY-LA levels. Additionally, functional enrichment and pathway analyses were done. (3) Three loci (DGKH, DCAF5, and LINC02261) were associated with NPY-LA levels (p-value < 1.5 × 10−6), which indicates an association with neurologic and vascular disorders. SNPs associated with variations in expression levels were found in six genes (including DCAF5). The pathway analysis showed that NPY-LA was associated with changes in gene tran-scription, protein modification, immunological functions, and the MAPK pathway. (4) Conclu-sively, we found NPY-LA to be significantly associated with three loci (DGKH, DCAF5, and LINC02261), and based on our findings we hypothesize that the presence of NPY-LA is associated with the regulation of the immune system and possibly neurologic and vascular disorders.
Originalsprog | Engelsk |
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Artikelnummer | 869 |
Tidsskrift | Genes |
Vol/bind | 13 |
Udgave nummer | 5 |
ISSN | 2073-4425 |
DOI | |
Status | Udgivet - 2022 |
Bibliografisk note
Funding Information:
This research was partly funded by the Poul and Erna Sehested Hansen Fund and the research council at Herlev and Gentofte Hospital. Furthermore, the study is part of the DiaUnion collaborative study, which is co-financed by EU Interreg ÖKS, Capital Region of Denmark, Region Skåne, Lund University, Steno Diabetes Center Copenhagen, and the Novo Nordisk Foundation (NYPS 20203388; NNF20SA0066296).
Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
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