Abstract
Untargeted metabolomics is a well-established technique and a powerful tool to find potential plasma biomarkers for early diagnosing hereditary transthyretin amyloidosis. Hereditary transthyretin amyloidosis (ATTRv) is a disabling and fatal disease with different clinical features such as polyneuropathy, cardiomyopathy, different gastrointestinal symptoms and renal failure. Plasma specimens collected from 27 patients with ATTRv (ATTRV30M), 26 asymptomatic TTRV30M carriers and 26 control individuals were subjected to gas chromatography (GC)- and liquid chromatography (LC)-mass spectrometry (MS)-based metabolomics analysis. Partial least squares discriminant and univariate analysis was used to analyse the data. The models constructed by Partial least squares-discriminant analysis (PLS-DA) could clearly discriminate ATTRV30M patients from controls and asymptomatic TTRV30M carriers. In total, 24 plasma metabolites (VIP > 1.0 and p < .05) were significantly altered in ATTRV30M patient group (6 increased and 18 decreased). Eleven of these distinguished the ATTRV30M group from both controls and TTRV30M carriers. Plasma metabolomics analysis revealed marked changes in several pathways in patients with ATTRV30M amyloidosis. Statistical analysis identified a panel of biomarkers that could effectively separate controls/TTRV30M carriers from ATTRV30M patients. These biomarkers can potentially be used to diagnose patients at an early stage of the disease.
Highlights
Transthyretin (TTR) amyloidosis is either inherited or acquired
This study aimed to identify candidate biomarkers by a metabolomics approach using mass spectrometry (MS)based methods, gas chromatography (GC/MS) and liquid chromatography (LC)/MS, in ATTRV30M amyloidosis patients for more objective phenotyping and potential candidates for early diagnosis of the disease
All ATTRV30M patient samples and a proportion of the samples in both the asymptomatic TTRV30M and control groups were obtained from the Amyloidosis Centre collection at Umeå University hospital, and the remaining samples were obtained from Northern Sweden Health and Disease Study (NSHDS) at Northern Sweden Medical Biobank Umeå, registration number 472
Summary
Transthyretin (TTR) amyloidosis is either inherited or acquired. Hereditary transthyretin (ATTRv) amyloidosis is an autosomal dominant inherited disease. More than 120 mutations in the TTR gene have been reported, and the majority is associated with the development of systemic amyloidosis. The TTR V30M is the most prevalent variant in Sweden. The phenotypic expression of ATTRv amyloidosis varies between different mutations, and within the same mutation. The most common manifestations of the disease are peripheral axonal neuropathy and/or cardiomyopathy [1,2]. Mutations characterised by central nervous manifestations of the disease, often in combination with ocular symptoms (oculoleptomeningeal) have been recognised [3]
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