Background: While numerous allergy-related biomarkers and targeted treatment strategies have been developed and employed, there are still signifcant limitations and challenges in the early diagnosis and targeted treatment for allegic diseases. Our study aims to identify circulating proteins causally associated with allergic disease-related traits through Mendelian randomization (MR)-based analytical framework.
Methods: Large-scale cis-MR was employed to estimate the effects of thousands of plasma proteins on five main allergic diseases. Additional analyses including MR Steiger analyzing and Bayesian colocalisation, were performed to test the robustness of the associations; These findings were further validated utilizing meta-analytical methods in the replication analysis. Both proteome- and transcriptome-wide association studies approach was applied, and then, a protein-protein interaction was conducted to examine the interplay between the identified proteins and the targets of existing medications.
Results: Eleven plasma proteins were identified with links to atopic asthma (AA), atopic dermatitis (AD), and allergic rhinitis (AR). Subsequently, these proteins were classified into four distinct target groups, with a focus on tier 1 and 2 targets due to their higher potential to become drug targets. MR analysis and extra validation revealed STAT6 and TNFRSF6B to be Tier 1 and IL1RL2 and IL6R to be Tier 2 proteins with the potential for AA treatment. Two Tier 1 proteins, CRAT and TNFRSF6B, and five Tier 2 proteins, ERBB3, IL6R, MMP12, ICAM1, and IL1RL2, were linked to AD, and three Tier 2 proteins, MANF, STAT6, and TNFSF8, to AR.
Conclusion: Eleven Tier 1 and 2 protein targets that are promising drug target candidates were identified for AA, AD, and AR, which influence the development of allergic diseases and expose new diagnostic and therapeutic targets.
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http://dx.doi.org/10.1186/s12864-024-10412-0 | DOI Listing |
Hum Genomics
January 2025
Department of Endocrine and Metabolic Diseases, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China.
Background: The molecular genetic diagnosis of congenital adrenal hyperplasia (CAH) is very challenging due to the high homology between the CYP21A2 gene and its pseudogene CYP21A1P.
Methodology: This study aims to assess the clinical efficacy of targeted long-read sequencing (T-LRS) by comparing it with a control method based on the combined assay (NGS, Multiplex ligation-dependent probe amplification and Sanger sequencing) and to introduce T-LRS as a first-tier diagnostic test for suspected CAH patients to improve the precise diagnosis of CAH.
Results: A large cohort of 562 participants including 322 probands and 240 family members was enrolled for the perspective (96 probands) and prospective study (226 probands).
J Transl Med
January 2025
Department of Gastroenterology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100730, China.
Background: Mounting evidence suggests that Parkinson's disease (PD) and inflammatory bowel disease (IBD) are closely associated and becoming global health burdens. However, the causal relationships and common pathogeneses between them are uncertain. Furthermore, they are uncurable.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Department of Anatomy, Dokkyo Medical University School of Medicine, 880 Kita-Kobayashi, Mibu-machi, Shimotsuga-gun 321-0293, Tochigi, Japan.
Biomedicines
December 2024
Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN 55905, USA.
Background/objectives: The enzyme ubiquitin-specific protease 44 (USP44) is a deubiquitinating enzyme with identified physiological roles as a tumor suppressor and an oncogene. While some binding partners and substrates are known for USP44, the identification of other interactions may improve our understanding of its role in cancer. We therefore performed a proximity biotinylation study that identified products of several known cancer genes that are associated with USP44, including a novel interaction between BRCA2 and USP44.
View Article and Find Full Text PDFBMJ Open Qual
January 2025
Rectorate, University of Health Sciences, Phnom Penh, Cambodia.
Rapid antigen diagnostic tests (Ag-RDTs) that quickly and accurately identify SARS-CoV-2 are an essential part of the COVID-19 response, but multiple factors can affect the validity of Ag-RDTs results. In Cambodia, several commercial Ag-RDTs have become available since the COVID-19 outbreak, but quality control (QC) and external quality assurance (EQA) of these rapid tests have yet to be fully and systematically implemented. We collaborated with laboratory experts in Australia and piloted an EQA programme of the commonly used COVID-19 Ag-RDTs at the University of Health Sciences' MERIEUX Laboratory (Tier 1 site-responsible for the in-country receipt and distribution of QA material) and four other participating laboratories (Tier 2-healthcare facility based) between November 2021 and November 2022.
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