Fibrinogen-beta gene haplotype is associated with mortality in sepsis

J Infect. 2007 Jun;54(6):572-7. doi: 10.1016/j.jinf.2006.10.001. Epub 2006 Nov 20.


Objectives: Fibrinogen plays a key role in coagulation and inflammation. Transcription of the fibrinogen-beta gene (FGB) is the rate-limiting step in fibrinogen production. Our aim was to determine whether haplotypes of FGB are associated with mortality and organ dysfunction in a cohort of patients with sepsis.

Methods: A prospective cohort of 631 consecutive Caucasian patients with sepsis from a tertiary care medical-surgical ICU were enrolled in a gene association study. Patients were genotyped for three polymorphisms in FGB: -854 G/A, -455 G/A, and +9006 G/A. Haplotypes were inferred using PHASE. The primary outcome was mortality. Secondary outcomes were severity of organ dysfunction as measured by days alive and free (DAF) of organ dysfunction.

Results: Haplotype GAA was associated with a significantly lower 28-day mortality (28.9% vs. 36.9% for all other haplotypes, p=0.03). Carriers of two copies of haplotype GAA (vs. one and zero copies) had more DAF of organ dysfunction. In a multivariate analysis, haplotype GAA was an independent predictor for lower mortality (OR=0.66, 95% CI=0.46-0.94, p=0.02).

Conclusions: Haplotype GAA in FGB is associated with lower mortality and lower severity of organ dysfunction. Haplotype GAA encompasses a previously described haplotype -1420A/-854G/-455A/-249C/-148T/+1690G that is associated with higher fibrinogen levels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Analysis of Variance
  • Chi-Square Distribution
  • Cohort Studies
  • Female
  • Fibrinogen / genetics*
  • Gene Frequency
  • Genotype
  • Haplotypes*
  • Humans
  • Male
  • Middle Aged
  • Outcome Assessment, Health Care
  • Polymorphism, Single Nucleotide
  • Sepsis / genetics*
  • Sepsis / mortality*


  • Fibrinogen