YKL-40 and Alcoholic Liver and Pancreas Damage and Disease in 86258 Individuals from the General Population: Cohort and Mendelian Randomization Studies

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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 journalJournal articleResearchpeer-review

Harvard

Kjaergaard, AD, Bojesen, SE, Nordestgaard, BG & Johansen, JS 2014, 'YKL-40 and Alcoholic Liver and Pancreas Damage and Disease in 86258 Individuals from the General Population: Cohort and Mendelian Randomization Studies', Clinical Chemistry, vol. 60, no. 11, pp. 1429-40. https://doi.org/10.1373/clinchem.2014.229096

APA

Kjaergaard, A. D., Bojesen, S. E., Nordestgaard, B. G., & Johansen, J. S. (2014). YKL-40 and Alcoholic Liver and Pancreas Damage and Disease in 86258 Individuals from the General Population: Cohort and Mendelian Randomization Studies. Clinical Chemistry, 60(11), 1429-40. https://doi.org/10.1373/clinchem.2014.229096

Vancouver

Kjaergaard AD, Bojesen SE, Nordestgaard BG, Johansen JS. YKL-40 and Alcoholic Liver and Pancreas Damage and Disease in 86258 Individuals from the General Population: Cohort and Mendelian Randomization Studies. Clinical Chemistry. 2014 Nov;60(11):1429-40. https://doi.org/10.1373/clinchem.2014.229096

Author

Kjaergaard, Alisa D ; Bojesen, Stig E ; Nordestgaard, Børge G ; Johansen, Julia S. / YKL-40 and Alcoholic Liver and Pancreas Damage and Disease in 86258 Individuals from the General Population : Cohort and Mendelian Randomization Studies. In: Clinical Chemistry. 2014 ; Vol. 60, No. 11. pp. 1429-40.

Bibtex

@article{d7ca8abec0ad49759e2a20b9dabec502,
title = "YKL-40 and Alcoholic Liver and Pancreas Damage and Disease in 86258 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.",
keywords = "Adipokines, Adult, Aged, Biological Markers, Cohort Studies, DNA, Denmark, Female, Genotype, Humans, Lectins, Liver Diseases, Alcoholic, Male, Middle Aged, Pancreatitis, Alcoholic, Polymerase Chain Reaction, Prospective Studies, Questionnaires, Random Allocation, Regression Analysis, Young Adult",
author = "Kjaergaard, {Alisa D} and Bojesen, {Stig E} and Nordestgaard, {B{\o}rge G} and Johansen, {Julia S}",
note = "{\circledC} 2014 American Association for Clinical Chemistry.",
year = "2014",
month = "11",
doi = "10.1373/clinchem.2014.229096",
language = "English",
volume = "60",
pages = "1429--40",
journal = "Clinical Chemistry",
issn = "0009-9147",
publisher = "American Association for Clinical Chemistry, Inc.",
number = "11",

}

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