Elevated plasma fibrinogen gamma' concentration is associated with myocardial infarction: effects of variation in fibrinogen genes and environmental factors.
BACKGROUND
Fibrinogen gamma', a fibrinogen gamma-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 gamma' concentration and examined the relationship between this variant and risk of myocardial infarction (MI).


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 gamma' 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 gamma' 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 gamma' concentration proved to be an independent predictor of MI [adjusted odds ratio (OR) (95% CI): 1.24 (1.01, 1.52)]. The plasma fibrinogen gamma' 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 gamma' 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.
Mannila
M N
MN
Department of Medicine, Atherosclerosis Research Unit, King Gustaf V Research Institute, Karolinska Institutet, Solna, Sweden. maria.nastase.mannila@ki.se
Lovely
R S
RS
Kazmierczak
S C
SC
Eriksson
P
P
Samnegård
A
A
Farrell
D H
DH
Hamsten
A
A
Silveira
A
A
D005260:Female; D005337:Fibrin / Q000737:chemistry; D005340:Fibrinogen / Q000737:chemistry / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008957:Models, Genetic; D009203:Myocardial Infarction / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood* / Q000235:genetics*; D011110:Polymorphism, Genetic; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000378:metabolism; D012306:Risk; D012307:Risk Factors
C115499:BBeta fibrinogen; C427756:P2-C protein, fibrinogen; D010446:Peptide Fragments; D020033:Protein Isoforms; D012333:RNA, Messenger; C464794:fibrinogen Aalpha; D005337:Fibrin; D005340:Fibrinogen