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The Capital Region of Denmark - a part of Copenhagen University Hospital
E-pub ahead of print

Elevated plasma YKL-40 and risk of infectious disease: a prospective study of 94665 individuals from the general population

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OBJECTIVES: YKL-40 is an acute phase protein elevated in patients with infectious and inflammatory diseases. We tested the hypothesis that baseline elevated YKL-40 is associated with increased risk of future infectious disease in healthy individuals in the general population.

METHODS: We followed prospectively 94665 individuals from the Danish general population for up to 23 years and analyzed for plasma YKL-40 levels (n=21584) and CHI3L1 rs4950928 genotype (n=94184). Endpoints were any infection, bacterial pneumonia, urinary tract infection, skin infection, sepsis, diarrhoeal disease, and other infections.

RESULTS: For YKL-40 percentile category 91-100% versus 0-33%, the multifactorially and C-reactive protein (CRP) adjusted hazard ratios were 1.71 (95% confidence interval: 1.50-1.96; P-value=4x10-14) for any infection, 1.97 (1.64-2.37; P=4x10-13) for bacterial pneumonia, 1.62 (1.24-2.11; P=0.002) for urinary tract infection, 1.74 (1.31-2.32;P=2x10-4) for skin infection, 1.76 (1.25-2.46; P=0.004) for sepsis, 1.90 (1.29-2.78; P=0.002) for diarrhoeal disease, and 2.71 (1.38-5.35; P=0.01) for other infections. In multifactorially and CRP adjusted models, a two-fold increase in YKL-40 was associated with increased risk of all infectious disease endpoints. Mendelian randomization did not support causality, as CHI3L1 rs4950928 was associated with 94% and 190% higher YKL-40 levels (for CG and CC versus GG genotype), but not with increased risk of any infectious disease endpoint.

CONCLUSIONS: Baseline elevated plasma YKL-40 was not a cause, but a strong marker of increased risk of future infectious diseases in individuals in the general population.

Original languageEnglish
JournalClinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases
ISSN1198-743X
DOIs
Publication statusE-pub ahead of print - 20 Jan 2020

ID: 59349082