title: YKL-40 and alcoholic liver and pancreas damage and disease in 86,258 individuals from the general population: cohort and mendelian randomization studies.
abstract: BACKGROUND
  We tested the hypothesis that observationally and genetically increased YKL-40 concentrations are associated with alcoholic liver and pancreas damage and disease.
  
  
  METHODS
  We performed cohort and mendelian randomization in 86,258 individuals from the Danish general population, with measured concentrations of plasma YKL-40 (n = 21 646) and CHI3L1 rs4950928 genotype (n = 84 738).
  
  
  RESULTS
  Increased YKL-40 was associated with increased alanine aminotransferase, bilirubin, alkaline phosphatase, γ-glutamyl transferase, erythrocyte mean corpuscular volume, C-reactive protein, and fibrinogen and with decreased albumin; coagulation factors II, VII, and X; and pancreatic amylase. The multifactorially adjusted hazard ratio for alcoholic liver cirrhosis comparing the 96%-100% vs 0%-33% YKL-40 percentile categories was 41 (95% CI 14-118). Corresponding ratios were 7.9 (5.1-12) for any alcoholic liver disease, 4.1 (1.7-10) for alcoholic pancreatitis, and 3.4 (1.9-6.1) for any pancreatitis. CHI3L1 rs4950928 genotype explained 14% of the variation in plasma YKL-40 concentrations but was not associated with alcoholic liver and pancreas damage or disease. A doubling in YKL-40 concentrations was associated with a multifactorially adjusted observational hazard ratio of 2.8 (2.4-3.3) for alcoholic liver cirrhosis and a corresponding genetic odds ratio of 1.1 (0.7-1.5). Corresponding risk estimates were 2.0 (1.8-2.2) observationally and 1.0 (0.8-1.1) genetically for any alcoholic liver disease, 1.4 (1.1-1.9) observationally and 1.1 (0.8-1.5) genetically for alcoholic pancreatitis, and 1.3 (1.1-1.6) observationally and 1.0 (0.8-1.3) genetically for any pancreatitis. Excessive alcohol consumption combined with YKL-40 concentrations in the top 5% was associated with 10-year risk of alcoholic liver cirrhosis of up to 7% in ever-smokers and 2% in never-smokers.
  
  
  CONCLUSIONS
  YKL-40 concentration within the top 5% was a marker for alcoholic liver cirrhosis, with no evidence to support a causal relationship.
authors.affiliation: Department of Clinical Biochemistry, Herlev Hospital, Faculty of Health and Medical Sciences, The Copenhagen General Population Study, Herlev University Hospital.
authors.forename: Alisa D
authors.initials: AD
authors.lastname: Kjaergaard
authors.affiliation: Department of Clinical Biochemistry, Herlev Hospital, Faculty of Health and Medical Sciences, The Copenhagen General Population Study, Herlev University Hospital, The Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen University Hospital.
authors.forename: Stig E
authors.initials: SE
authors.lastname: Bojesen
authors.affiliation: Department of Clinical Biochemistry, Herlev Hospital, Faculty of Health and Medical Sciences, The Copenhagen General Population Study, Herlev University Hospital, The Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen University Hospital.
authors.forename: Børge G
authors.initials: BG
authors.lastname: Nordestgaard
authors.affiliation: Faculty of Health and Medical Sciences, Department of Medicine, Herlev Hospital, and Department of Oncology, Herlev Hospital, Copenhagen University Hospital, University of Copenhagen, Denmark. julia.johansen@post3.tele.dk.
authors.forename: Julia S
authors.initials: JS
authors.lastname: Johansen
mesh_terms: D054392:Adipokines / Q000097:blood*; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D000071451:Chitinase-3-Like Protein 1; D015331:Cohort Studies; D004247:DNA / Q000737:chemistry / Q000235:genetics; D003718:Denmark / Q000453:epidemiology; D005260:Female; D005838:Genotype; D006801:Humans; D037102:Lectins / Q000097:blood*; D008108:Liver Diseases, Alcoholic / Q000097:blood* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D019512:Pancreatitis, Alcoholic / Q000097:blood* / Q000235:genetics; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D011897:Random Allocation; D012044:Regression Analysis; D011795:Surveys and Questionnaires; D055815:Young Adult
chemical_list: D054392:Adipokines; D015415:Biomarkers; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D037102:Lectins; D004247:DNA