Fibrinogen genes modify the fibrinogen response to ambient particulate matter.

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 microm (PM(10)) and plasma fibrinogen levels. The PM(10)-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.

[Risk factors of chronic obstructive pulmonary disease]. / Fattori di rischio per broncopneumopatia cronica ostruttiva.

Many personal and environmental risk factors are associated to increased prevalence and severity of chronic obstructive pulmonary disease (COPD). In this review, we shortly describe most of these risk factors, aiming at defining each factor as causative or modifier of the natural history of the disease. It is clear that the environmental risk factors do have an outstanding relevance for both the initiation and the evolution of COPD. This review focuses on the crucial importance of prevention in order to decrease the public health burden of COPD in the western countries during the next decades.