C reactive protein and chronic obstructive pulmonary disease: a Mendelian randomisation approach

TY - JOUR

T1 - C reactive protein and chronic obstructive pulmonary disease

T2 - a Mendelian randomisation approach

AU - Dahl, Morten

AU - Vestbo, Jørgen

AU - Zacho, Jeppe

AU - Lange, Peter

AU - Tybjærg-Hansen, Anne

AU - Nordestgaard, Børge G

PY - 2011/3

Y1 - 2011/3

N2 - Background: It is unclear whether elevated plasma C reactive protein (CRP) is causally related to chronic obstructive pulmonary disease (COPD). The authors tested the hypothesis that genetically elevated plasma CRP causes COPD using a Mendelian randomisation design. Methods: The authors measured high-sensitivity CRP in plasma, genotyped for four single nucleotide polymorphisms in the CRP gene, and screened for spirometry-defined COPD and hospitalisation due to COPD in 7974 individuals from the Copenhagen City Heart Study and in 32 652 individuals from the Copenhagen General Population Study. Results: Elevated plasma CRP >3 mg/l compared with <1 mg/l was associated with risk estimates of 1.8 and 2.8 for spirometry-based COPD and of 1.6 and 1.8 for hospitalisation due to COPD in the Copenhagen City Heart Study and the Copenhagen General Population Study, respectively. Genotype combinations of the four CRP polymorphisms were associated with up to a 62% increase in plasma CRP. However, these genotype combinations did not associate with increased risk of COPD or hospitalisation due to COPD in either cohort or in the two cohorts combined. On instrumental variable analysis, a doubling of plasma CRP versus a doubling of genetically elevated CRP resulted in ORs for COPD of 1.27 (95% CI 1.25 to 1.30) versus 1.01 (0.81 to 1.26) and for COPD hospitalisation of 1.47 (1.43 to 1.51) versus 0.82(0.59 to 1.13). Conclusion: Although elevated CRP is related to both a diagnosis of COPD and subsequent hospital admission, genetically elevated plasma CRP is not associated with an increased risk of clinical COPD. This suggests that the association between CRP levels and COPD is not causal.

AB - Background: It is unclear whether elevated plasma C reactive protein (CRP) is causally related to chronic obstructive pulmonary disease (COPD). The authors tested the hypothesis that genetically elevated plasma CRP causes COPD using a Mendelian randomisation design. Methods: The authors measured high-sensitivity CRP in plasma, genotyped for four single nucleotide polymorphisms in the CRP gene, and screened for spirometry-defined COPD and hospitalisation due to COPD in 7974 individuals from the Copenhagen City Heart Study and in 32 652 individuals from the Copenhagen General Population Study. Results: Elevated plasma CRP >3 mg/l compared with <1 mg/l was associated with risk estimates of 1.8 and 2.8 for spirometry-based COPD and of 1.6 and 1.8 for hospitalisation due to COPD in the Copenhagen City Heart Study and the Copenhagen General Population Study, respectively. Genotype combinations of the four CRP polymorphisms were associated with up to a 62% increase in plasma CRP. However, these genotype combinations did not associate with increased risk of COPD or hospitalisation due to COPD in either cohort or in the two cohorts combined. On instrumental variable analysis, a doubling of plasma CRP versus a doubling of genetically elevated CRP resulted in ORs for COPD of 1.27 (95% CI 1.25 to 1.30) versus 1.01 (0.81 to 1.26) and for COPD hospitalisation of 1.47 (1.43 to 1.51) versus 0.82(0.59 to 1.13). Conclusion: Although elevated CRP is related to both a diagnosis of COPD and subsequent hospital admission, genetically elevated plasma CRP is not associated with an increased risk of clinical COPD. This suggests that the association between CRP levels and COPD is not causal.

KW - Adult

KW - Aged

KW - Biological Markers

KW - C-Reactive Protein

KW - Cohort Studies

KW - Denmark

KW - Female

KW - Forced Expiratory Volume

KW - Genotype

KW - Hospitalization

KW - Humans

KW - Male

KW - Mendelian Randomization Analysis

KW - Middle Aged

KW - Polymorphism, Single Nucleotide

KW - Pulmonary Disease, Chronic Obstructive

U2 - 10.1136/thx.2009.131193

DO - 10.1136/thx.2009.131193

M3 - Journal article

C2 - 21059738

SN - 0040-6376

VL - 66

SP - 197

EP - 204

JO - Thorax

JF - Thorax

IS - 3

ER -