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.
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.
Bereczky
Zsuzsanna
Z
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.
Balogh
Emilia
E
Katona
Eva
E
Pocsai
Zsuzsa
Z
Czuriga
István
I
Széles
György
G
Kárpáti
Levente
L
Adány
Róza
R
Edes
István
I
Muszbek
László
L
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
D021122:Protein Subunits; D005340:Fibrinogen; D005176:Factor XIII