title: Common genetic polymorphisms and haplotypes of fibrinogen alpha, beta, and gamma chains affect fibrinogen levels and the response to proinflammatory stimulation in myocardial infarction survivors: the AIRGENE study.
abstract: OBJECTIVE
  This study was designed to investigate whether single nucleotide polymorphisms (SNPs) and haplotypes of the fibrinogen gene-cluster (fibrinogen chains alpha [FGA], beta [FGB], and gamma [FGG]) could explain the inter- and intraindividual variability of fibrinogen levels in patients with atherosclerosis. We also searched for genetic determinants affecting the responses of fibrinogen genes to proinflammatory stimulation.
  
  
  BACKGROUND
  The mechanisms regulating fibrinogen levels are not fully understood, and they are likely to be regulated by complex gene-environment interactions.
  
  
  METHODS
  In the AIRGENE study, 895 survivors of myocardial infarction from 5 European cities were followed prospectively for 6 to 8 months, and plasma fibrinogen, interleukin (IL)-6, and C-reactive protein levels were determined monthly. We analyzed 21 SNPs and the corresponding haplotypes in the 3 fibrinogen genes.
  
  
  RESULTS
  Eight SNPs in FGA and FGB were significantly associated with fibrinogen levels. Similarly, 2 different haplotypes in FGA and 3 in FGB were also associated with mean fibrinogen levels. The IL-6 levels had a significant impact on the associations between SNPs/haplotypes in FGA/FGB and fibrinogen levels. We also identified SNPs and haplotypes in FGA and FGB with strong impact on the intraindividual variability of fibrinogen during the follow-up period.
  
  
  CONCLUSIONS
  We identified common SNPs and haplotypes on FGA/FGB genes, explaining the interindividual and intraindividual variability of fibrinogen levels, in patients with a history of myocardial infarction. We have also identified for the first time, SNPs/haplotypes on FGA/FGB whose effects on fibrinogen expression are modified by the underlying IL-6 levels. These findings may have an impact on risk stratification and the design of genetically guided therapeutic approaches in patients with advanced atherosclerosis.
authors.affiliation: Centre for Environmental Research, Municipal Institute of Medical Research, Barcelona, Spain.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Jacquemin
authors.forename: Charalambos
authors.initials: C
authors.lastname: Antoniades
authors.forename: Fredrik
authors.initials: F
authors.lastname: Nyberg
authors.forename: Estel
authors.initials: E
authors.lastname: Plana
authors.forename: Martina
authors.initials: M
authors.lastname: Müller
authors.forename: Sonja
authors.initials: S
authors.lastname: Greven
authors.forename: Veikko
authors.initials: V
authors.lastname: Salomaa
authors.forename: Jordi
authors.initials: J
authors.lastname: Sunyer
authors.forename: Tom
authors.initials: T
authors.lastname: Bellander
authors.forename: Alexandros-Georgios
authors.initials: AG
authors.lastname: Chalamandaris
authors.forename: Ricardo
authors.initials: R
authors.lastname: Pistelli
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Koenig
authors.forename: Annette
authors.initials: A
authors.lastname: Peters
mesh_terms: D000368:Aged; D002097:C-Reactive Protein / Q000378:metabolism*; D005340:Fibrinogen / Q000235:genetics* / Q000378:metabolism; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics
chemical_list: D015850:Interleukin-6; D005340:Fibrinogen; D002097:C-Reactive Protein