© 1995 American Heart Association, Inc.
Articles |
Gender-Related Association Between ß-Fibrinogen Genotype and Plasma Fibrinogen Levels and Linkage Disequilibrium at the Fibrinogen Locus in Greenland Inuit
From the Gaubius Laboratory TNO-PG, Leiden, the Netherlands (M.P.M. de M., P. de K., C.K.); the Institute for Thrombosis Research, South Jutland University Centre, Esbjerg, Denmark (M.P.M. de M., J.J.); and The Rayne Institute, Department of Medicine, University College London Medical School, London, UK (F.R.G., A.E.T.).
Correspondence to M.P.M. de Maat, Gaubius Laboratory TNO-PG, PO Box 2215, 2301 CE Leiden, Netherlands.
Abstract Elevated plasma fibrinogen levels represent
an increased risk for cardiovascular disease, but the
mechanism explaining this association is still not clear. Genetic
differences may play a role, because it has been shown that individuals
who carry the rare alleles of polymorphisms in the genes for
the Bß-chain (Bcl I and G/A-455) and the
A
-chain (Taq I) of fibrinogen have higher plasma
fibrinogen levels and that patients with peripheral
arterial disease have a higher frequency of the rare
allele of the Bcl I polymorphism than do healthy
control subjects. We studied the Greenland Inuit, a population with a
low incidence of ischemic heart disease; polymorphisms of
the fibrinogen gene; and their association with plasma fibrinogen
level. The group studied had a small age range (30 to 34 years), 97%
were smokers, 62 were men, and 71 were women. We observed that in the
Inuit, frequencies of the rare alleles of the ß gene and of the
common alleles of the gene polymorphisms were lower than
those published for other populations (all Caucasian). Accordingly, in
the Inuit, these distribution patterns give a higher frequency of
alleles that are associated with lower plasma fibrinogen levels. We
further observed comparable linkage disequilibrium between and ß
gene polymorphisms in Caucasian populations. In Inuit men the rare
allele of the Bcl I and G/A-455 fibrinogen
polymorphisms was associated with plasma fibrinogen level
comparable with the association described in Caucasian populations. In
women, however, we did not find a significant association, supporting
the desirability of separate data analysis for men and women of
the influence of genetic factors on atherosclerotic disease. In
conclusion, in the Inuit the association of fibrinogen
polymorphisms with fibrinogen levels is comparable with that in
Caucasians, but the genes that are associated with lower fibrinogen
levels are more frequent in the Inuit than in Caucasians.
Key Words: fibrinogen • Inuit • cardiovascular risk indicators • DNA polymorphism
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