Genetic variation in the fibrinogen-alpha and fibrinogen-gamma genes in relation to arterial stiffness: the Rotterdam Study.
OBJECTIVE
Arterial stiffness increases with age and predicts cardiovascular disease. Fibrinogen is an acute-phase protein and some studies showed an association with arterial stiffness. We studied genetic variation in the fibrinogen-alpha (FGA) and fibrinogen-gamma (FGG) genes, by means of single nucleotide polymorphisms (FGA: -58 G/A, 1374 G/A, 1526 T/C, 312 Thr/Ala, and FGG: 4288 G/A, 6326 G/A, 7792 T/C) and resultant haplotypes in relation to arterial stiffness.


METHODS
The present study (n = 3891) was embedded in the Rotterdam Study. Associations of the fibrinogen level, genotypes and haplotypes with aortic stiffness (pulse wave velocity), carotid stiffness (distensibility coefficient) and pulse pressure were investigated in men and women by analyses of variance, linear regression and by haplotype analyses. Analyses were adjusted for age, mean arterial pressure, heart rate, known cardiovascular risk factors and atherosclerosis.


RESULTS
Genotype analyses yielded associations of FGA-58 G/A (P = 0.040, for trend) and FGA-1526 T/C (P = 0.004, for trend) with the fibrinogen levels, but no consistent associations with arterial stiffness, in women. FGA-haplotype 4 was associated with the fibrinogen level (P = 0.02) in women. FGA-haplotype 3 and FGG-haplotype 2 were associated with aortic stiffness (P = 0.05) in women. No associations were found in men.


CONCLUSIONS
Findings indicate that the fibrinogen level and genetic variation in the FGA and FGG genes may influence arterial stiffness in women.
Department of Epidemiology & Biostatistics, Erasmus Medical Center, Rotterdam, The Netherlands.
Mark P S
MP
Sie
Aaron
A
Isaacs
Moniek P M
MP
de Maat
Francesco U S
FU
Mattace-Raso
André G
AG
Uitterlinden
Isabella
I
Kardys
Albert
A
Hofman
Arnold P G
AP
Hoeks
Robert S
RS
Reneman
Cornelia M
CM
van Duijn
Jaqueline C M
JC
Witteman
D000368:Aged; D001158:Arteries / Q000503:physiopathology*; D003187:Compliance; D005260:Female; D005340:Fibrinogen / Q000235:genetics*; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide
D005340:Fibrinogen