Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.
Policlinic of Prosthetic Dentistry, Gerodontology and Biomaterials, Center of Oral Health, University Medicine Greifswald, Greifswald, Germany.
Bone. 2020 Dec;141:115675. doi: 10.1016/j.bone.2020.115675. Epub 2020 Oct 6.
YKL-40, also known as chitinase-3-like protein 1, is a new proinflammatory biomarker, that might play a role in tissue remodeling and bone resorption. Here we evaluated the associations of the YKL-40 plasma concentration with heel ultrasound parameters and bone turnover markers (BTMs) in adult men and women from the general population. We tested for a causal role of YKL-40 on bone metabolism using published single nucleotide polymorphisms (SNPs) with consequences for YKL-40 expression and function.
Data were obtained from two population-based cohorts: the Study of Health in Pomerania (SHIP) and SHIP-Trend. Quantitative ultrasound (QUS) measurements at the heel were performed and bone turnover was assessed by measurement of intact amino-terminal propeptide of type I procollagen (PINP) and carboxy-terminal telopeptide of type I collagen (CTX). Associations between the YKL-40 plasma concentration and the QUS-based parameters, bone turnover marker (BTM) concentrations and 44 SNPs, including the lead SNP rs4950928, were evaluated in 382 subjects. Furthermore, we assessed the associations between the same SNPs and the QUS-based parameters (n = 5777) or the BTM concentrations (n = 7190).
Sex-specific linear regression models adjusted for a comprehensive panel of interfering covariantes revealed statistically significant inverse associations between YKL-40 and all QUS-based parameters as well as positive associations with CTX in women. The rs4950928 polymorphism was associated with YKL-40 in men and women but none of the tested SNPs was associated with the QUS-based parameters or the BTMs after correction for multiple testing.
Plasma YKL-40 concentrations are associated with QUS-based parameters as well as CTX concentrations in women but these associations are probably not causal.
YKL-40 又称几丁质酶 3 样蛋白 1，是一种新的促炎生物标志物，可能在组织重塑和骨吸收中发挥作用。本研究评估了 YKL-40 血浆浓度与普通人群中成年男性和女性足跟超声参数和骨转换标志物（BTM）的相关性。我们使用已发表的与 YKL-40 表达和功能相关的单核苷酸多态性（SNP），测试了 YKL-40 对骨代谢的因果作用。
数据来自两个基于人群的队列：波美拉尼亚健康研究（SHIP）和 SHIP-Trend。对足跟进行定量超声（QUS）测量，并通过测量Ⅰ型前胶原氨基端肽（PINP）和Ⅰ型胶原羧基端肽（CTX）来评估骨转换。在 382 名受试者中，评估了 YKL-40 血浆浓度与基于 QUS 的参数、骨转换标志物（BTM）浓度和包括 lead SNP rs4950928 在内的 44 个 SNP 之间的相关性。此外，我们评估了相同 SNP 与基于 QUS 的参数（n=5777）或 BTM 浓度（n=7190）之间的相关性。
调整了综合干扰协变量的性别特异性线性回归模型显示，YKL-40 与所有基于 QUS 的参数呈统计学上显著的负相关，与女性的 CTX 呈正相关。rs4950928 多态性与男性和女性的 YKL-40 相关，但在进行多次测试校正后，没有一个测试 SNP 与基于 QUS 的参数或 BTMs 相关。
血浆 YKL-40 浓度与女性的基于 QUS 的参数和 CTX 浓度相关，但这些关联可能不是因果关系。
