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Systemic inflammation, genetic susceptibility and lung function

¹ Centre for Environmental Epidemiological Research and ² Municipal Institute of Medical Research, Universitat Pompeu Fabra, CIBERESP, Barcelona, Spain. ³ Catholic University and ⁷ Local Health Authority, Rome, Italy. ⁴ GSF-National Research Centre for Environment and Health, Institute of Epidemiology, Neuherberg and ⁵ University of Ulm Medical Center, Ulm, Germany, ⁶ National Public Health Institute (KTL), Helsinki, Finland.

CORRESPONDENCE: J. Sunyer, Centre for Environmental Epidemiological Research, Municipal Institute of Medical Research, Dr Aiguader 88, 08003 Barcelona, Spain. Fax: 34 933160575. E-mail: jsunyer{at}imim.es

Keywords: C-reactive protein, genes, lung function, Mendelian randomisation

Received: May 3, 2007
Accepted March 17, 2008

Local inflammation in airway diseases is well recognised, but less is known about the association between low-grade systemic inflammatory processes and lung function. The aim of the present study was to assess the association between inflammatory markers and lung function, taking into account polymorphisms in genes coding for inflammatory markers.

In 134 post-myocardial infarction patients, six repeated measurements of C-reactive protein (CRP), interleukin (IL)-6 and fibrinogen in peripheral blood were assayed using high-sensitivity tests. Spirometry was conducted at baseline. Genotyping of single nucleotide polymorphisms was performed in genes coding for the inflammatory markers.

CRP and IL-6 levels were negatively associated with forced expiratory volume in one second (FEV₁), forced vital capacity (FVC) and mean forced expiratory flow between 25 and 75% of FVC (FEF_25–75%). In the CRP gene, both the polymorphism rs1205 and the haplotype 2 showed a protective association with FEV₁ and FEF_25–75%, and, to a lesser extent, with FVC. rs1205 and haplotype 2 were both negatively associated with CRP levels in peripheral blood. Analysis with instrumental variables also showed a protective effect between these CRP gene polymorphisms and lung function.

Results are very suggestive that heritability of lung function is at least partly controlled by the CRP gene. Applying a Mendelian randomisation approach, the study supports a causal association between low-grade general inflammation and airway diseases.