基质金属蛋白酶降解的I型胶原与变异和临床前痴呆相关。
Matrix metalloproteinase-degraded type I collagen is associated with variants and preclinical dementia.
作者信息
Tang Man-Hung Eric, Blair Joseph P M, Bager Cecilie Liv, Bay-Jensen Anne-Christine, Henriksen Kim, Christiansen Claus, Karsdal Morten Asser
机构信息
ProScion (M.-H.E.T., J.P.M.B., C.L.B.), Herlev; Faculty of Health and Medical Sciences (J.P.M.B.), University of Copenhagen; ImmunoScience (A.-C.B.-J., C.C., M.A.K.), and Endocrinology (K.H.), Nordic Bioscience, Biomarkers and Research, Herlev, Denmark.
出版信息
Neurol Genet. 2020 Sep 10;6(5):e508. doi: 10.1212/NXG.0000000000000508. eCollection 2020 Oct.
OBJECTIVE
Dysregulation 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.
METHODS
Patient 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.
RESULTS
Twenty-two genome-wide significant variants associated with C1M were identified in the / gene cluster. The / 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.
CONCLUSIONS
Our study provides elements for better understanding the role of the collagen metabolism in the onset of cognitive impairment.
目的
I型胶原蛋白代谢失调对人类健康有重大影响。我们之前发现基质金属蛋白酶降解的I型胶原蛋白（C1M）与过早死亡及年龄相关病理状况有关。为剖析I型胶原蛋白失调的生物学影响，我们对与I型胶原蛋白周转相关的遗传因素进行了全基因组筛选。
方法
收集了总共4981名丹麦绝经后女性的患者登记数据和基因型。评估了与C1M血清水平的全基因组关联，并进行了表型-基因型关联分析。
结果
在/基因簇中鉴定出22个与C1M相关的全基因组显著变异。/基因簇与高脂血症和认知障碍有关，我们进一步发现C1M水平与tau降解标志物相关，且在临床前认知障碍女性中降低。
结论
我们的研究为更好地理解胶原蛋白代谢在认知障碍发病中的作用提供了依据。
Zotero 插件