YKL-40 and Alcoholic Liver and Pancreas Damage and Disease in 86258 Individuals from the General Population: Cohort and Mendelian Randomization Studies
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
YKL-40 and Alcoholic Liver and Pancreas Damage and Disease in 86258 Individuals from the General Population : Cohort and Mendelian Randomization Studies. / Kjaergaard, Alisa D; Bojesen, Stig E; Nordestgaard, Børge G; Johansen, Julia S.
In: Clinical Chemistry, Vol. 60, No. 11, 11.2014, p. 1429-40.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - YKL-40 and Alcoholic Liver and Pancreas Damage and Disease in 86258 Individuals from the General Population
T2 - Cohort and Mendelian Randomization Studies
AU - Kjaergaard, Alisa D
AU - Bojesen, Stig E
AU - Nordestgaard, Børge G
AU - Johansen, Julia S
N1 - © 2014 American Association for Clinical Chemistry.
PY - 2014/11
Y1 - 2014/11
N2 - 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.
AB - 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.
KW - Adipokines
KW - Adult
KW - Aged
KW - Biological Markers
KW - Cohort Studies
KW - DNA
KW - Denmark
KW - Female
KW - Genotype
KW - Humans
KW - Lectins
KW - Liver Diseases, Alcoholic
KW - Male
KW - Middle Aged
KW - Pancreatitis, Alcoholic
KW - Polymerase Chain Reaction
KW - Prospective Studies
KW - Questionnaires
KW - Random Allocation
KW - Regression Analysis
KW - Young Adult
U2 - 10.1373/clinchem.2014.229096
DO - 10.1373/clinchem.2014.229096
M3 - Journal article
C2 - 25225167
VL - 60
SP - 1429
EP - 1440
JO - Clinical Chemistry
JF - Clinical Chemistry
SN - 0009-9147
IS - 11
ER -
ID: 137203364