The Journal of clinical endocrinology and metabolism · 2025
Circulating Micro-RNAs in Patients With Hypophosphatasia: Results of the First Micro-RNA Analysis in HPP.
СтатьяНаблюдательное исследованиеНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Haschka Judith, Messner Zora, Feurstein Julia, Hadzimuratovic Benjamin, Zwerina Jochen, Diendorfer Andreas B, Pultar Marianne, Hackl Matthias, Kuzma Martin, Payer Juraj, Resch Heinrich, Kocijan Roland
Аннотация
INTRODUCTION: Adult hypophosphatasia (HPP) patients present with diffuse heterogenous symptoms often mimicking rheumatological diseases or osteoporosis and therefore accompanied by delayed diagnosis. The aim of this study was to identify circulating microRNAs (miRNAs) in adult HPP patients and to identify potential associations with clinical patients' characteristics.
METHODS: We utilized untargeted miRNA biomarker discovery by small RNA-sequencing to investigate cell-free miRNA profiles in 24 adult HPP patients (pathogenic variant of the ALPL gene, HPP-related clinical symptoms, and repeatedly low alkaline phosphatase) and 24 healthy controls (CTRL).
RESULTS: Patients and CTRL were comparable in age (47.9 ± 14.2 vs 45.9 ± 8.8 years, P = .980) and sex (55.5% vs 47.8% females, P = 1.000). In total, 91% of patients reported musculoskeletal pain, 41% diffuse neurological symptoms, and 64% history of fractures. In total, 84 miRNAs were significantly differently expressed between HPP and CTRL in next-generation sequencing analysis (P < .05). Of these, 14 miRNAs were selected (selection criteria: P < .05, tissue specificity index >0.7, log2 fold change >+0.8 or <-0.8) for validation using RT-qualitative PCR, which verified 6 of 14 selected miRNAs (P < .05; miR-122-3p, miR-140-5p, miR-143-3p, miR-155-5p, miR-451a, miR-92a-3p). Target prediction and enrichment analysis identified associations with the musculoskeletal system and the central nervous system. In total, 37 miRNAs correlated with alkaline phosphatase levels, but only 3 miRNAs with pyridoxal-5'-phosphate.
CONCLUSION: These findings highlight a profound involvement of multiple organ systems and the potential of miRNAs as biomarkers for the effect of HPP on various systems.
CLINICAL TRIALS NO: NCT04018287.
METHODS: We utilized untargeted miRNA biomarker discovery by small RNA-sequencing to investigate cell-free miRNA profiles in 24 adult HPP patients (pathogenic variant of the ALPL gene, HPP-related clinical symptoms, and repeatedly low alkaline phosphatase) and 24 healthy controls (CTRL).
RESULTS: Patients and CTRL were comparable in age (47.9 ± 14.2 vs 45.9 ± 8.8 years, P = .980) and sex (55.5% vs 47.8% females, P = 1.000). In total, 91% of patients reported musculoskeletal pain, 41% diffuse neurological symptoms, and 64% history of fractures. In total, 84 miRNAs were significantly differently expressed between HPP and CTRL in next-generation sequencing analysis (P < .05). Of these, 14 miRNAs were selected (selection criteria: P < .05, tissue specificity index >0.7, log2 fold change >+0.8 or <-0.8) for validation using RT-qualitative PCR, which verified 6 of 14 selected miRNAs (P < .05; miR-122-3p, miR-140-5p, miR-143-3p, miR-155-5p, miR-451a, miR-92a-3p). Target prediction and enrichment analysis identified associations with the musculoskeletal system and the central nervous system. In total, 37 miRNAs correlated with alkaline phosphatase levels, but only 3 miRNAs with pyridoxal-5'-phosphate.
CONCLUSION: These findings highlight a profound involvement of multiple organ systems and the potential of miRNAs as biomarkers for the effect of HPP on various systems.
CLINICAL TRIALS NO: NCT04018287.