title: Contribution of haplotypes across the fibrinogen gene cluster to variation in risk of myocardial infarction.
abstract: Fibrinogen has consistently been recognized as an independent predictor of myocardial infarction (MI). Multiple mechanisms link fibrinogen to MI; therefore disentangling the factors underlying variation in plasma fibrinogen concentration is essential. Candidate regions in the fibrinogen gamma (FGG), alpha (FGA) and beta (FGB) genes were screened for single nucleotide polymorphisms (SNPs). Several novel SNPs were detected in the FGG and FGA genes in addition to the previously known SNPs in the fibrinogen genes. Tight linkage disequilibrium extending over various physical distances was observed between most SNPs. Consequently, eight SNPs were chosen and determined in 377 postinfarction patients and 387 healthy individuals. None of the SNPs were associated with plasma fibrinogen concentration or MI. Haplotype analyses revealed a consistent pattern of haplotypes associated with variation in risk of MI. Of the four haplotypes inferred using the FGA -58G>A and FGG 1299 +79T>C SNPs, the most frequent haplotype, FGG-FGA*1 (prevalence 46.6%), was associated with increased risk of MI (OR 1.51; 95%CI 1.18, 1.93), whereas the least frequent haplotype, FGG-FGA*4 (11.8%), was associated with lower risk of MI (OR 0.79 95%CI 0.64, 0.98). In conclusion, fibrinogen haplotypes, but not SNPs in isolation, are associated with variation in risk of MI.
authors.affiliation: Atherosclerosis Research Unit, Karolinska Institutet, King Gustaf V Research Institute, Karolinska University Hospital, Solna, Stockholm, Sweden. Maria.Nastase.Mannila@medks.ki.se
authors.forename: Maria Nastase
authors.initials: MN
authors.lastname: Mannila
authors.forename: Per
authors.initials: P
authors.lastname: Eriksson
authors.forename: Pia
authors.initials: P
authors.lastname: Lundman
authors.forename: Ann
authors.initials: A
authors.lastname: Samnegård
authors.forename: Susanna
authors.initials: S
authors.lastname: Boquist
authors.forename: Carl-Göran
authors.initials: CG
authors.lastname: Ericsson
authors.forename: Per
authors.initials: P
authors.lastname: Tornvall
authors.forename: Anders
authors.initials: A
authors.lastname: Hamsten
authors.forename: Angela
authors.initials: A
authors.lastname: Silveira
mesh_terms: D016022:Case-Control Studies; D005260:Female; D005340:Fibrinogen / Q000032:analysis / Q000235:genetics*; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D005810:Multigene Family; D009203:Myocardial Infarction / Q000209:etiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012306:Risk
chemical_list: D005340:Fibrinogen