Systemic inflammation, genetic susceptibility and lung function

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

^* To whom correspondence should be addressed. E-mail: jsunyer{at}imim.es.

	Abstract

Local inflammation in airway diseases is well recognized, but less in known about the association between low-grade systemic inflammatory processes and lung function. Our aim is 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 6 (IL-6) and fibrinogen in peripheral blood were assayed using high-sensitivity tests (n=741). Spirometry was conducted at baseline. Genotyping of single nucleotide polymorphisms (SNPs) was performed in genes coding for the inflammatory markers.

CRP and IL6 levels were negatively associated with FEV₁, FVC and FEF_25–75. CRP gene (both the polymorphism rs1205 and the haplotype 2 in this gene) 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 (p=0.05).

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