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.

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.

Twenty-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.

Our study provides elements for better understanding the role of the collagen metabolism in the onset of cognitive impairment.

I型胶原代谢失调对人体健康有很大影响。我们之前已经看到基质金属蛋白酶降解的 I 型胶原蛋白 (C1M) 与早逝和年龄相关的病理有关。为了剖析 I 型胶原蛋白失调的生物学影响，我们对与 I 型胶原蛋白更新相关的遗传因素进行了全基因组筛选。

共收集了 4,981 名丹麦绝经后妇女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。

在APOE-C1 / TOMM40基因簇中鉴定了 22 个与 C1M 相关的全基因组显着变异。APOE-C1 / TOMM40基因簇与高脂血症和认知障碍相关，我们进一步发现 C1M 水平与 tau 降解标志物相关，并且在临床前认知障碍的女性中降低。

我们的研究为更好地理解胶原代谢在认知障碍发病中的作用提供了要素。