Associations of plasma YKL-40 concentrations with heel ultrasound parameters and bone turnover markers in the general adult population

Steinke, Jörn; Samietz, Stefanie; Friedrich, Nele; Weiss, Stefan; Michalik, Stephan; Biffar, Reiner; Nauck, Matthias; Völker, Uwe; Wallaschofski, Henri; Pietzner, Maik; Hannemann, Anke

Affiliations

¹Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany

²Policlinic of Prosthetic Dentistry, Gerodontology and Biomaterials, Center of Oral Health, University Medicine Greifswald, Greifswald, Germany

³DZHK (German Centre for Cardiovascular Research), Partner Site Greifswald, University Medicine, Greifswald, Germany

⁴Interfaculty Institute for Genetics and Functional Genomics, University Medicine and University of Greifswald, Greifswald, Germany

Abstract and keywords

Objective: 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.

Methods: 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).

Results: 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.

Conclusions: Plasma YKL-40 concentrations are associated with QUS-based parameters as well as CTX concentrations in women but these associations are probably not causal.

Keywords: YKL-40; CHI3L1; Bone stiffness index; Bone turnover; Osteoporosis

Links

DOI: 10.1016/j.bone.2020.115675

PubMed: 33031973

WoS: 000601334100006

History

Received: 2020-08-25

Revised: 2020-10-1

Accepted: 2020-10-1

Online: 2020-10-6

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