Elevated plasma fibrinogen γ′ concentration is associated with myocardial infarction: Effects of variation in fibrinogen genes and environmental factors

Maria Nastase Mannila, R. S. Lovely, Steven (Steve) Kazmierczak, P. Eriksson, A. Samnegård, David Farrell, A. Hamsten, A. Silveira

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Abstract

Background: Fibrinogen γ′, a fibrinogen γ-chain variant generated via alternative mRNA processing, has been associated with susceptibility to thrombotic disease. Objective: The present case-control study searched for potential determinants of the plasma fibrinogen γ′ concentration and examined the relationship between this variant and risk of myocardial infarction (MI). Patients and methods: The Stockholm Coronary Artery Risk Factor study, comprising 387 postinfarction patients and 387 healthy individuals, was employed. The fibrinogen gamma (FGG) 9340T > C [rs1049636], fibrinogen alpha (FGA) 2224G > A [rs2070011] and fibrinogen beta (FGB) 1038G > A [rs1800791] polymorphisms were determined. The plasma fibrinogen γ′ concentration was measured by enzyme-linked immunosorbent assay. The multifactor dimensionality reduction method was used for interaction analyses on risk of MI. Results: The FGG 9340T > C and FGA 2224G > A polymorphisms, total plasma concentrations of fibrinogen, insulin and high-density lipoprotein, and gender appeared to be independent determinants of plasma fibrinogen γ′ concentration in patients, and the corresponding determinants in controls included FGG 9340T > C and FGA 2224G > A polymorphisms and plasma fibrinogen concentration. An elevated plasma fibrinogen γ′ concentration proved to be an independent predictor of MI [adjusted odds ratio (OR) (95% CI): 1.24 (1.01, 1.52)]. The plasma fibrinogen γ′ concentration was involved in a high-order interaction with total plasma fibrinogen and the FGG 9340T > C and FGA 2224G > A polymorphisms, associated with a further increased risk of MI [OR (95% CI): 3.22 (2.35, 4.39)]. Conclusions: Plasma fibrinogen γ′ concentration influences the risk of MI, and this relationship seems to be strengthened by the presence of an elevated total plasma fibrinogen concentration and the FGG 9340T and FGA 2224G alleles.

Original languageEnglish (US)
Pages (from-to)766-773
Number of pages8
JournalJournal of Thrombosis and Haemostasis
Volume5
Issue number4
DOIs
Publication statusPublished - Apr 2007

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Keywords

  • Fibrinogen γ′
  • Fibrinogen polymorphisms
  • Interaction
  • Myocardial infarction

ASJC Scopus subject areas

  • Medicine(all)

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