A COMMON MUTATION (G(-455)-]A) IN THE BETA-FIBRINOGEN PROMOTER IS AN INDEPENDENT PREDICTOR OF PLASMA-FIBRINOGEN, BUT NOT OF ISCHEMIC-HEART-DISEASE - A STUDY OF 9,127 INDIVIDUALS BASED ON THE COPENHAGEN CITY HEART-STUDY

A common mutation (G(-455)-->A) in the promoter region of the beta-fib rinogen gene has been associated with elevated plasma fibrinogen level s. Whether fibrinogen genotype affects plasma fibrinogen levels and ri sk of ischemic heart disease in the general population has not been st udied. We investigated the association between fibrinogen genotype, pl asma fibrinogen levels, and ischemic heart disease in a general popula tion sample (n = 9,127). The A-allele (relative frequency, 0.20) was a ssociated with elevated plasma fibrinogen levels in both genders (P < 0.001). While the effect of the A-allele on fibrinogen level was addit ive in men, the effect was dominant in postmenopausal women. The A-all ele raising effect appeared to be two- to threefold greater in individ uals with ischemic heart disease than in those without. An increase of 1 SD in plasma fibrinogen increased the odds ratio for ischemic heart disease by similar to 20% (P < 0.01 for women and < 0.005 for men). H owever, the frequency of the A-allele was similar in those with and wi thout ischemic heart disease, and genotype was not a predictor of dise ase. These results demonstrate that the (G(-455)-->A) mutation in the promoter region of the beta-fibrinogen gene is associated with an incr ease in plasma fibrinogen in both genders in the general population. T his increase does not appear to cause ischemic heart disease.