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Plasma urate, lung function and chronic obstructive pulmonary disease: a Mendelian randomisation study in 114 979 individuals from the general population

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@article{e4111b86e81f45b49de8765a5aff5c2f,
title = "Plasma urate, lung function and chronic obstructive pulmonary disease: a Mendelian randomisation study in 114 979 individuals from the general population",
abstract = "BACKGROUND: Urate is a strong antioxidant in plasma and may protect against lung function impairment. We tested the hypothesis that high plasma urate is causally associated with better lung function and low risk of respiratory symptoms and COPD.METHODS: We measured lung function and plasma urate in 114 979 individuals from the Copenhagen City Heart Study and the Copenhagen General Population Study and genotyped for SLC2A9 rs7442295 and ABCG2 rs2231142 variants, previously associated with high plasma urate, in 110 152 individuals.RESULTS: In the two studies combined, multivariable-adjusted 100 µmol/L higher plasma urate was associated with -1.54{\%} (95{\%} CI -1.67 to -1.40) lower FEV1 {\%} predicted and -1.57{\%} (95{\%} CI -1.69 to -1.44) lower FVC {\%} predicted observationally; the corresponding estimates for genetically determined 100 µmol/L higher plasma urate were -0.46{\%} (95{\%} CI -1.17 to 0.25) and -0.40{\%} (95{\%} CI -1.03 to 0.23). High plasma urate was also associated with higher risk of respiratory symptoms; however, genetically determined high plasma urate was not associated with respiratory symptoms. Finally, we identified 14 151 individuals with COPD and found ORs of 1.08 (95{\%} CI 1.06 to 1.11) for COPD observationally and 1.01 (95{\%} CI 0.88 to 1.15) genetically per 100 µmol/L higher plasma urate.CONCLUSION: High plasma urate was associated with worse lung function and higher risk of respiratory symptoms and COPD in observational analyses; however, genetically high plasma urate was not associated with any of these outcomes. Thus, our data do not support a direct causal relationship.",
keywords = "Aged, Biomarkers/blood, Denmark, Female, Genetic Variation, Genotype, Humans, Male, Middle Aged, Predictive Value of Tests, Pulmonary Disease, Chronic Obstructive/blood, Respiratory Function Tests, Risk Factors, Uric Acid/blood",
author = "Kobylecki, {Camilla J} and Signe Vedel-Krogh and Shoaib Afzal and Nielsen, {Sune F} and Nordestgaard, {B{\o}rge G}",
note = "{\circledC} Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.",
year = "2018",
month = "8",
doi = "10.1136/thoraxjnl-2017-210273",
language = "English",
volume = "73",
pages = "748--757",
journal = "Thorax",
issn = "0040-6376",
publisher = "B M J Group",
number = "8",

}

RIS

TY - JOUR

T1 - Plasma urate, lung function and chronic obstructive pulmonary disease

T2 - a Mendelian randomisation study in 114 979 individuals from the general population

AU - Kobylecki, Camilla J

AU - Vedel-Krogh, Signe

AU - Afzal, Shoaib

AU - Nielsen, Sune F

AU - Nordestgaard, Børge G

N1 - © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

PY - 2018/8

Y1 - 2018/8

N2 - BACKGROUND: Urate is a strong antioxidant in plasma and may protect against lung function impairment. We tested the hypothesis that high plasma urate is causally associated with better lung function and low risk of respiratory symptoms and COPD.METHODS: We measured lung function and plasma urate in 114 979 individuals from the Copenhagen City Heart Study and the Copenhagen General Population Study and genotyped for SLC2A9 rs7442295 and ABCG2 rs2231142 variants, previously associated with high plasma urate, in 110 152 individuals.RESULTS: In the two studies combined, multivariable-adjusted 100 µmol/L higher plasma urate was associated with -1.54% (95% CI -1.67 to -1.40) lower FEV1 % predicted and -1.57% (95% CI -1.69 to -1.44) lower FVC % predicted observationally; the corresponding estimates for genetically determined 100 µmol/L higher plasma urate were -0.46% (95% CI -1.17 to 0.25) and -0.40% (95% CI -1.03 to 0.23). High plasma urate was also associated with higher risk of respiratory symptoms; however, genetically determined high plasma urate was not associated with respiratory symptoms. Finally, we identified 14 151 individuals with COPD and found ORs of 1.08 (95% CI 1.06 to 1.11) for COPD observationally and 1.01 (95% CI 0.88 to 1.15) genetically per 100 µmol/L higher plasma urate.CONCLUSION: High plasma urate was associated with worse lung function and higher risk of respiratory symptoms and COPD in observational analyses; however, genetically high plasma urate was not associated with any of these outcomes. Thus, our data do not support a direct causal relationship.

AB - BACKGROUND: Urate is a strong antioxidant in plasma and may protect against lung function impairment. We tested the hypothesis that high plasma urate is causally associated with better lung function and low risk of respiratory symptoms and COPD.METHODS: We measured lung function and plasma urate in 114 979 individuals from the Copenhagen City Heart Study and the Copenhagen General Population Study and genotyped for SLC2A9 rs7442295 and ABCG2 rs2231142 variants, previously associated with high plasma urate, in 110 152 individuals.RESULTS: In the two studies combined, multivariable-adjusted 100 µmol/L higher plasma urate was associated with -1.54% (95% CI -1.67 to -1.40) lower FEV1 % predicted and -1.57% (95% CI -1.69 to -1.44) lower FVC % predicted observationally; the corresponding estimates for genetically determined 100 µmol/L higher plasma urate were -0.46% (95% CI -1.17 to 0.25) and -0.40% (95% CI -1.03 to 0.23). High plasma urate was also associated with higher risk of respiratory symptoms; however, genetically determined high plasma urate was not associated with respiratory symptoms. Finally, we identified 14 151 individuals with COPD and found ORs of 1.08 (95% CI 1.06 to 1.11) for COPD observationally and 1.01 (95% CI 0.88 to 1.15) genetically per 100 µmol/L higher plasma urate.CONCLUSION: High plasma urate was associated with worse lung function and higher risk of respiratory symptoms and COPD in observational analyses; however, genetically high plasma urate was not associated with any of these outcomes. Thus, our data do not support a direct causal relationship.

KW - Aged

KW - Biomarkers/blood

KW - Denmark

KW - Female

KW - Genetic Variation

KW - Genotype

KW - Humans

KW - Male

KW - Middle Aged

KW - Predictive Value of Tests

KW - Pulmonary Disease, Chronic Obstructive/blood

KW - Respiratory Function Tests

KW - Risk Factors

KW - Uric Acid/blood

U2 - 10.1136/thoraxjnl-2017-210273

DO - 10.1136/thoraxjnl-2017-210273

M3 - Journal article

VL - 73

SP - 748

EP - 757

JO - Thorax

JF - Thorax

SN - 0040-6376

IS - 8

ER -

ID: 56616549