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β2-Adrenergic genotypes and risk of severe exacerbations in COPD: a prospective cohort study

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@article{259358facd1c42aea3a68a6523f8fb7d,
title = "β2-Adrenergic genotypes and risk of severe exacerbations in COPD: a prospective cohort study",
abstract = "BACKGROUND: Individual susceptibility to exacerbations in chronic obstructive pulmonary disease (COPD) is likely influenced by genetic factors; however, most such variance is unexplained. We hypothesised that β2-adrenergic receptor genotypes, Gly16Arg (rs1042713, c.46G>A) and Gln27Glu (rs1042714, c.79C>G) influence risk of severe exacerbations in COPD.METHODS: Among 96 762 individuals in the Copenhagen General Population Study, we identified 5262 with COPD (forced expiratory volume in one second divided by forced vital capacity, FEV1/FVC, below 0.7, FEV1 less than 80{\%} of predicted value, age above 40 years and no asthma) who had genotyping performed. Severe exacerbations were defined as acute admissions due to COPD during 5 years of follow-up (mean 3.4 years). 923 individuals with COPD diagnosed similarly in the Copenhagen City Heart Study (CCHS) were used for replication analyses.RESULTS: We recorded 461 severe exacerbations in 5262 subjects. The HRs for severe exacerbations were 1.62 (95{\%} CI 1.30 to 2.03, p=0.00002) for 16Gly/Arg heterozygotes and 1.41 (1.04 to 1.91, p=0.03) for 16Arg homozygotes, compared with 16Gly homozygotes. HRs were 1.35 (1.03 to 1.76, p=0.03) for 27Gln/Glu heterozygotes and 1.49 (1.12 to 1.98, p=0.006) for 27Gln homozygotes, compared with 27Glu homozygotes. Similar trends were observed in the CCHS. Among 27Gln homozygotes only, HRs were 5.20 (1.81 to 14.9, p=0.002) for 16Gly/Arg heterozygotes and 4.03 (1.40 to 11.6, p=0.01) for 16Arg homozygotes, compared with 16Gly homozygotes.CONCLUSION: Common β2-adrenergic receptor genotypes influence risk of severe exacerbations in COPD, potentially mainly by genetic influence of the 16Arg allele in rs1042713.",
keywords = "adrenoreceptor polymorphisms, COPD, precision medicine",
author = "Ingebrigtsen, {Truls Sylvan} and J{\o}rgen Vestbo and Line Rode and Marott, {Jacob Louis} and Peter Lange and Nordestgaard, {B{\o}rge G}",
note = "{\circledC} Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.",
year = "2019",
month = "10",
doi = "10.1136/thoraxjnl-2018-212340",
language = "English",
volume = "74",
pages = "934--940",
journal = "Thorax",
issn = "0040-6376",
publisher = "B M J Group",
number = "10",

}

RIS

TY - JOUR

T1 - β2-Adrenergic genotypes and risk of severe exacerbations in COPD

T2 - a prospective cohort study

AU - Ingebrigtsen, Truls Sylvan

AU - Vestbo, Jørgen

AU - Rode, Line

AU - Marott, Jacob Louis

AU - Lange, Peter

AU - Nordestgaard, Børge G

N1 - © Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.

PY - 2019/10

Y1 - 2019/10

N2 - BACKGROUND: Individual susceptibility to exacerbations in chronic obstructive pulmonary disease (COPD) is likely influenced by genetic factors; however, most such variance is unexplained. We hypothesised that β2-adrenergic receptor genotypes, Gly16Arg (rs1042713, c.46G>A) and Gln27Glu (rs1042714, c.79C>G) influence risk of severe exacerbations in COPD.METHODS: Among 96 762 individuals in the Copenhagen General Population Study, we identified 5262 with COPD (forced expiratory volume in one second divided by forced vital capacity, FEV1/FVC, below 0.7, FEV1 less than 80% of predicted value, age above 40 years and no asthma) who had genotyping performed. Severe exacerbations were defined as acute admissions due to COPD during 5 years of follow-up (mean 3.4 years). 923 individuals with COPD diagnosed similarly in the Copenhagen City Heart Study (CCHS) were used for replication analyses.RESULTS: We recorded 461 severe exacerbations in 5262 subjects. The HRs for severe exacerbations were 1.62 (95% CI 1.30 to 2.03, p=0.00002) for 16Gly/Arg heterozygotes and 1.41 (1.04 to 1.91, p=0.03) for 16Arg homozygotes, compared with 16Gly homozygotes. HRs were 1.35 (1.03 to 1.76, p=0.03) for 27Gln/Glu heterozygotes and 1.49 (1.12 to 1.98, p=0.006) for 27Gln homozygotes, compared with 27Glu homozygotes. Similar trends were observed in the CCHS. Among 27Gln homozygotes only, HRs were 5.20 (1.81 to 14.9, p=0.002) for 16Gly/Arg heterozygotes and 4.03 (1.40 to 11.6, p=0.01) for 16Arg homozygotes, compared with 16Gly homozygotes.CONCLUSION: Common β2-adrenergic receptor genotypes influence risk of severe exacerbations in COPD, potentially mainly by genetic influence of the 16Arg allele in rs1042713.

AB - BACKGROUND: Individual susceptibility to exacerbations in chronic obstructive pulmonary disease (COPD) is likely influenced by genetic factors; however, most such variance is unexplained. We hypothesised that β2-adrenergic receptor genotypes, Gly16Arg (rs1042713, c.46G>A) and Gln27Glu (rs1042714, c.79C>G) influence risk of severe exacerbations in COPD.METHODS: Among 96 762 individuals in the Copenhagen General Population Study, we identified 5262 with COPD (forced expiratory volume in one second divided by forced vital capacity, FEV1/FVC, below 0.7, FEV1 less than 80% of predicted value, age above 40 years and no asthma) who had genotyping performed. Severe exacerbations were defined as acute admissions due to COPD during 5 years of follow-up (mean 3.4 years). 923 individuals with COPD diagnosed similarly in the Copenhagen City Heart Study (CCHS) were used for replication analyses.RESULTS: We recorded 461 severe exacerbations in 5262 subjects. The HRs for severe exacerbations were 1.62 (95% CI 1.30 to 2.03, p=0.00002) for 16Gly/Arg heterozygotes and 1.41 (1.04 to 1.91, p=0.03) for 16Arg homozygotes, compared with 16Gly homozygotes. HRs were 1.35 (1.03 to 1.76, p=0.03) for 27Gln/Glu heterozygotes and 1.49 (1.12 to 1.98, p=0.006) for 27Gln homozygotes, compared with 27Glu homozygotes. Similar trends were observed in the CCHS. Among 27Gln homozygotes only, HRs were 5.20 (1.81 to 14.9, p=0.002) for 16Gly/Arg heterozygotes and 4.03 (1.40 to 11.6, p=0.01) for 16Arg homozygotes, compared with 16Gly homozygotes.CONCLUSION: Common β2-adrenergic receptor genotypes influence risk of severe exacerbations in COPD, potentially mainly by genetic influence of the 16Arg allele in rs1042713.

KW - adrenoreceptor polymorphisms

KW - COPD

KW - precision medicine

UR - http://www.scopus.com/inward/record.url?scp=85072035770&partnerID=8YFLogxK

U2 - 10.1136/thoraxjnl-2018-212340

DO - 10.1136/thoraxjnl-2018-212340

M3 - Journal article

VL - 74

SP - 934

EP - 940

JO - Thorax

JF - Thorax

SN - 0040-6376

IS - 10

ER -

ID: 57916651