Matrix metalloproteinase-degraded type I collagen is associated with APOE/TOMM40 variants and preclinical dementia
| Autor: | Kim Henriksen, Anne-Christine Bay-Jensen, Joseph P.M. Blair, Cecilie L. Bager, Morten A. Karsdal, Claus Christiansen, Man-Hung Eric Tang |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Apolipoprotein E medicine.medical_specialty BIOMARKERS PROGRESSION Matrix (biology) Matrix metalloproteinase APOLIPOPROTEIN-E Article 03 medical and health sciences 0302 clinical medicine RISK-FACTOR Internal medicine Gene cluster Genotype Hyperlipidemia EXTRACELLULAR-MATRIX medicine FIBROSIS FRAGMENTS Genetics (clinical) Genetic association business.industry DEGRADATION medicine.disease 030104 developmental biology Endocrinology MARKER IMMUNE-SYSTEM Neurology (clinical) business 030217 neurology & neurosurgery Type I collagen |
| Zdroj: | Neurology: Genetics article-version (Version of Record) 3 Tang, M-H E, Blair, J P M, Bager, C L, Bay-Jensen, A-C, Henriksen, K, Christiansen, C & Karsdal, M A 2020, ' Matrix metalloproteinase-degraded type I collagen is associated with APOE/TOMM40 variants and preclinical dementia ', Neurology: Genetics, vol. 6, no. 5, 508 . https://doi.org/10.1212/NXG.0000000000000508 |
| ISSN: | 2376-7839 |
| Popis: | ObjectiveDysregulation of type I collagen metabolism has a great impact on human health. We have previously seen that matrix metalloproteinase–degraded type I collagen (C1M) is associated with early death and age-related pathologies. To dissect the biological impact of type I collagen dysregulation, we have performed a genome-wide screening of the genetic factors related to type I collagen turnover.MethodsPatient registry data and genotypes have been collected for a total of 4,981 Danish postmenopausal women. Genome-wide association with serum levels of C1M was assessed and phenotype-genotype association analysis performed.ResultsTwenty-two genome-wide significant variants associated with C1M were identified in the APOE-C1/TOMM40 gene cluster. The APOE-C1/TOMM40 gene cluster is associated with hyperlipidemia and cognitive disorders, and we further found that C1M levels correlated with tau degradation markers and were decreased in women with preclinical cognitive impairment.ConclusionsOur study provides elements for better understanding the role of the collagen metabolism in the onset of cognitive impairment. |
| Databáze: | OpenAIRE |
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