title: Modulation of the risk of coronary sclerosis/myocardial infarction by the interaction between factor XIII subunit A Val34Leu polymorphism and fibrinogen concentration in the high risk Hungarian population.
abstract: BACKGROUND
  The results on the association of factor XIII (FXIII) A subunit (FXIII-A) Val34Leu polymorphism with the risk of myocardial infarction (MI) are rather inconclusive. The original paper and confirmatory reports demonstrated a protective effect of the mutation, but results demonstrating the lack of protection have also been published. Gene-gene and gene-environmental interactions have been proposed to be responsible for the opposing results. As the rate of change in fibrin clot permeability with increasing fibrinogen concentrations decreased stepwise with increasing number of Leu34 alleles it was proposed that the protection by Val34Leu polymorphism become effective only at higher fibrinogen concentrations. However, this hypothesis has not been tested on patients with coronary artery disease.
  
  
  METHODS
  955 consecutive patients admitted for coronary angiography were categorized according to the presence or absence of significant coronary sclerosis (CS) and according to positive or negative history of MI. The frequency of FXIII-A Val34Leu polymorphism, and a number of risk factors, including fibrinogen were determined in the patients. FXIII-A Val34Leu polymorphism was also investigated in a population control group of 1146 subjects.
  
  
  RESULTS
  The presence of FXIII-A Leu34 allele or homozygous Leu34 genotype did not change the risk of CS or MI in the general Hungarian population. However, when patients with fibrinogen level in the upper quartile were separately investigated, the Leu34 allele provided a statistically significant protection against MI.
  
  
  CONCLUSIONS
  Fibrinogen concentration modulates the effect of Leu34 allele on the risk of MI; its protective effect emerges at increasing fibrinogen concentration.
authors.affiliation: Clinical Research Center, Haemostasis, Thrombosis and Vascular Biology Research Group of the Hungarian Academy of Sciences, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary.
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Bereczky
authors.forename: Emilia
authors.initials: E
authors.lastname: Balogh
authors.forename: Eva
authors.initials: E
authors.lastname: Katona
authors.forename: Zsuzsa
authors.initials: Z
authors.lastname: Pocsai
authors.forename: István
authors.initials: I
authors.lastname: Czuriga
authors.forename: György
authors.initials: G
authors.lastname: Széles
authors.forename: Levente
authors.initials: L
authors.lastname: Kárpáti
authors.forename: Róza
authors.initials: R
authors.lastname: Adány
authors.forename: István
authors.initials: I
authors.lastname: Edes
authors.forename: László
authors.initials: L
authors.lastname: Muszbek
mesh_terms: D001161:Arteriosclerosis; D003324:Coronary Artery Disease / Q000209:etiology*; D005176:Factor XIII / Q000235:genetics*; D005340:Fibrinogen / Q000032:analysis*; D006814:Hungary / Q000453:epidemiology; D017720:Molecular Epidemiology; D020125:Mutation, Missense; D009203:Myocardial Infarction / Q000209:etiology*; D011110:Polymorphism, Genetic; D021122:Protein Subunits / Q000235:genetics; D012306:Risk
chemical_list: D021122:Protein Subunits; D005340:Fibrinogen; D005176:Factor XIII