GENDER-RELATED ASSOCIATION BETWEEN BETA-FIBRINOGEN GENOTYPE AND PLASMA-FIBRINOGEN LEVELS AND LINKAGE DISEQUILIBRIUM AT THE FIBRINOGEN LOCUSIN GREENLAND INUIT

Elevated plasma fibrinogen levels represent an increased risk for card iovascular disease, but the mechanism explaining this association is s till not clear. Genetic differences may play a role, because it has be en shown that individuals who carry the rare alleles of polymorphisms in the genes for the B beta-chain (Bcl I and G/A-(455)) and the A alph a-chain (Taq I) of fibrinogen have higher plasma fibrinogen levels and that patients with peripheral arterial disease have a higher frequenc y of the rare allele of the Bcl I polymorphism than do healthy control subjects. We studied the Greenland Inuit, a population with a low inc idence of ischemic heart disease; polymorphisms of the fibrinogen gene ; and their association with plasma fibrinogen level. The group studie d had a small age range (30 to 34 years), 97% were smokers, 62 were me n, and 71 were women. We observed that in the Inuit, frequencies of th e rare alleles of the beta gene and of the common alleles of the alpha gene polymorphisms were lower than those published for other populati ons (all Caucasian). Accordingly, in the Inuit, these distribution pat terns give a higher frequency of alleles that are associated with lowe r plasma fibrinogen levels. We further observed comparable linkage dis equilibrium between alpha and beta gene polymorphisms in Caucasian pop ulations. In Inuit men the rare allele of the Bcl I and G/A-(455) fibr inogen polymorphisms was associated with plasma fibrinogen level compa rable with the association described in Caucasian populations. In wome n, however, we did not find a significant association, supporting the desirability of separate data analysis for men and women of the influe nce of genetic factors on atherosclerotic disease. In conclusion, in t he Inuit the association of fibrinogen polymorphisms with fibrinogen l evels is comparable with that in Caucasians, but the genes that are as sociated with lower fibrinogen levels are more frequent in the Inuit t han in Caucasians.