Matrix metalloproteinase-degraded type I collagen is associated with APOE/TOMM40 variants and preclinical dementia
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Matrix metalloproteinase-degraded type I collagen is associated with APOE/TOMM40 variants and preclinical dementia. / Tang, Man-Hung Eric; Blair, Joseph P. M.; Bager, Cecilie Liv; Bay-Jensen, Anne-Christine; Henriksen, Kim; Christiansen, Claus; Karsdal, Morten Asser.
In: Neurology: Genetics, Vol. 6, No. 5, 508, 2020.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Matrix metalloproteinase-degraded type I collagen is associated with APOE/TOMM40 variants and preclinical dementia
AU - Tang, Man-Hung Eric
AU - Blair, Joseph P. M.
AU - Bager, Cecilie Liv
AU - Bay-Jensen, Anne-Christine
AU - Henriksen, Kim
AU - Christiansen, Claus
AU - Karsdal, Morten Asser
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
KW - EXTRACELLULAR-MATRIX
KW - APOLIPOPROTEIN-E
KW - IMMUNE-SYSTEM
KW - RISK-FACTOR
KW - DEGRADATION
KW - PROGRESSION
KW - FIBROSIS
KW - BIOMARKERS
KW - FRAGMENTS
KW - MARKER
U2 - 10.1212/NXG.0000000000000508
DO - 10.1212/NXG.0000000000000508
M3 - Journal article
C2 - 33134509
VL - 6
JO - Neurology: Genetics
JF - Neurology: Genetics
SN - 2376-7839
IS - 5
M1 - 508
ER -
ID: 271502628