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Published ahead of print on January 8, 2009, doi:10.1164/rccm.200805-751OC
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American Journal of Respiratory and Critical Care Medicine Vol 179. pp. 484-491, (2009)
© 2009 American Thoracic Society
doi: 10.1164/rccm.200805-751OC

Original Article

Fibrinogen Genes Modify the Fibrinogen Response to Ambient Particulate Matter

Annette Peters1, Sonja Greven1,2, Iris M. Heid1,2, Fiammetta Baldari3, Susanne Breitner1, Tom Bellander4,5, Christina Chrysohoou6, Thomas Illig1, Bénédicte Jacquemin7, Wolfgang Koenig8, Timo Lanki9, Fredrik Nyberg4,10, Juha Pekkanen9, Riccardo Pistelli3, Regina Rückerl1, Christodoulos Stefanadis6, Alexandra Schneider1, Jordi Sunyer7,11,12 and H. Erich Wichmann1,2 for the AIRGENE Study Group*

1 Helmholtz Zentrum München-German Research Center for Environmental Health, Institute of Epidemiology, Neuherberg, Germany; 2 Ludwig-Maximilians University, Munich, Germany; 3 Catholic Hospital, Rome, Italy; 4 Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden; 5 Department of Occupational and Environmental Health, Stockholm County Council, Stockholm, Sweden; 6 Hippokrates Hospital, University of Athens, Athens, Greece; 7 Municipal Institute for Medical Research (IMIM), Barcelona, Spain; 8 Department of Cardiology, University of Ulm, Ulm, Germany; 9 Department of Environmental Health, National Public Health Institute (KTL), Kuopio, Finland; 10 AstraZeneca Research and Development, Mölndal, Sweden; 11 Center for Environmental Epidemiological Research (CREAL), Barcelona, Spain; and 12 El Centro de Investigación Biomédica en Red de Epidemiologia y Salud Pública (CIBERESP), Barcelona, Spain

Correspondence and requests for reprints should be addressed to Annette Peters, Ph.D., Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Epidemiology, Ingolstaedter Landstrasse, Neuherberg 85764, Germany. E-mail: peters{at}helmholtz-muenchen.de

Rationale: Ambient particulate matter has been associated with systemic inflammation indicated by blood markers such as fibrinogen, implicated in promoting atherothrombosis.

Objectives: This study evaluated whether single-nucleotide polymorphisms (SNPs) within the fibrinogen genes modified the relationship between ambient particles and plasma fibrinogen.

Methods: In 854 myocardial infarction survivors from five European cities plasma fibrinogen levels were determined repeatedly (n = 5,082). City-specific analyses were conducted to assess the impact of particulate matter on fibrinogen levels, applying additive mixed models adjusting for patient characteristics, time trend, and weather. City-specific estimates were pooled by meta-analysis methodology.

Measurements and Main Results: Seven SNPs in the FGA and FGB genes shown to be associated with differences in fibrinogen levels were selected. Promoter SNPs within FGA and FGB were associated with modifications of the relationship between 5-day averages of particulate matter with an aerodynamic diameter below 10 µm (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).

Conclusions: The data suggest that susceptibility to ambient particulate matter may be partly genetically determined by polymorphisms that alter early physiological responses such as transcription of fibrinogen. Subjects with variants of these frequent SNPs 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.

Key Words: air pollution • inflammation • genetic susceptibility • epidemiology • particulate matter


AT A GLANCE COMMENTARY

Scientific Knowledge on the Subject
Ambient particulate air pollution has been associated with inflammatory responses, but little is known about the extent to which individual responses vary due to genetic predisposition.

What This Study Adds to the Field
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.

 

Related articles in AJRCCM:

Breathe Deeply into Your Genes!: Genetic Variants and Air Pollution Effects
Andrea Baccarelli
AJRCCM 2009 179: 431-432. [Full Text]  



This article has been cited by other articles:


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 Am. J. Respir. Crit. Care Med.Home page
A. Baccarelli
Breathe Deeply into Your Genes!: Genetic Variants and Air Pollution Effects
Am. J. Respir. Crit. Care Med., March 15, 2009; 179(6): 431 - 432.
[Full Text] [PDF]


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