Highlights 2009:
Fibrinogen Genes Modify the Fibrinogen Response to Ambient Particulate Matter
Prof. Dr. Annette Peters, peters@helmholtz-zentrum.de, +49-(0)89-3187-4566 or -3626
Keywords:
Air pollution, epidemiology, gene-environment interaction, inflammation, particulate matter
Central statement:
Subjects with variants in the fibrinogen gene cluster may have increased risks not only due to constitutionally higher fibrinogen concentrations, but also due to an augmented response to environmental stimuli such as ambient particulate matter.
Highlight:
Ambient air pollution is still a major concern and European standard levels for particulate matter are repeatedly exceeded in winter time. Ambient particulate matter has been associated with systemic inflammation indicated by blood markers such as fibrinogen, implicated in promoting cardiovascular disease. This study evaluated in a multi-center European approach whether genetic variation within the fibrinogen genes modified the relationship between ambient particles and plasma fibrinogen. In 854 myocardial infarction survivors from five European cities plasma fibrinogen levels were determined repeatedly. Statistical analyses adjusted for patient characteristics, time trend, and weather. Promoter single-nucleotide polymorphisms (SNP) within the fibrinogen genes (FGA and FGB) were associated with modifications of the relationship between 5-day averages of particulate matter with an aerodynamic diameter below 10 mm (PM10) and plasma fibrinogen levels. The PM10–fibrinogen relationship for subjects with the homozygous minor allele genotype of FGB rs1800790 compared with subjects homozygous for the major allele was eightfold higher (P value for the interaction, 0.037). The data suggest that susceptibility to ambient particulate matter may be partly genetically determined by variations that alter early physiological responses such as transcription of fibrinogen. Subjects with variants of these genetic variants may have increased risks not only due to constitutionally higher fibrinogen concentrations, but also due to an augmented response to environmental inflammatory stimuli such as ambient particulate matter. Furthermore, the results indicate that the risk associated with air pollution may be larger in sub-populations than currently estimated.
Publication:
A. Peters, S. Greven, I. Heid, F. Baldari, S. Breitner, T. Bellander, C. Chrysohoon, T. Illig, B. Jacquemin, W. Koenig, T. Landi, F. Nyberg, J. Pekkanen, R. Pistelli, R. Rückerl, C. Stefanadis, A. Schneider, J. Sunyer, and H.-E. Wichmann. Fibrinogen Genes Modify the Fibrinogen Response to Ambient Particulate Matter. Am J Respir.Crit Care Med. 2009. Vol 179. 484–491.
Abstract
Taking account of the HMGU mission:
The study described here is how personal risk factors such as genes determine inflammatory responses to an environmental factor, namely particulate air pollution. Thereby the study elucidated how air pollution may affect a potentially vulnerable subgroup to air pollution effects within myocardial infarction survivors.