Title
Factor VII polymorphisms in populations with different risks of cardiovascular disease
Author
de Maat, M.P.M.
Green, F.
de Knijff, P.
Jespersen, J.
Kluft, C.
Gaubius Instituut TNO
Publication year
1997
Abstract
Increased plasma factor VII coagulant activity (FVII:C) has been associated with the risk of ischemic heart disease (IHD). Differences in plasma FVII:C among individuals are associated with three common polymorphisms in the FVII gene. Therefore, we investigated FVII polymorphisms in four populations that differ in their risk of developing cardiovascular disease, namely, Europeans, Greenland Inuit, Gujarati Indians, and Afro- caribbeans. We studied (1) the promoter polymorphism, which is the result of a decanucleotide insertion in the FVII promoter at position -323 from the start of translation; (2) the hypervariable region 4 polymorphism (HVR4), which is the result of a variable number of tandem repeats in intron 7; and (3) the RQ353 polymorphism, a guanine-to-adenine substitution in the position of the codon for amino acid 353 resulting in an amino acid replacement of arginine (R) by glutamine (Q) in the FVII protein. The frequencies of these three polymorphisms and their linkage disequilibrium were different in the four populations studied. The frequencies of the alleles associated with higher plasma FVII:C were lower in the Europeans than in the Inuit, a population with a lower incidence of IHD. There was an association between both the promoter polymorphism and the RQ353 polymorphism and the plasma FVII:C in the Europeans, the Inuit, and the Gujarati Indians, and an association only between the RQ353 polymorphism and plasma FVII:C in the Afro-caribbeans. Only in the Inuit was the HVR4 polymorphism associated with plasma FVII:C. In multiple regression analysis, the additional information provided by the promoter polymorphism when the other polymorphisms were already included in the model was the most pronounced, suggesting that the promoter polymorphism may be the functional mutation having the greatest effect on determining plasma FVII:C.
Subject
Biology
Factor VII polymorphisms
FVII:C
Ischemic heart disease
blood clotting factor 7
adult
amino acid sequence
article
caribbean islands
coronary risk
disease association
europe
female
genetic polymorphism
greenland
human
incidence
ischemic heart disease
major clinical study
male
priority journal
protein determination
race difference
risk assessment
Adult
Aged
Factor VII
Female
Humans
Male
Middle Aged
Myocardial Ischemia
Polymorphism, Genetic
Promoter Regions (Genetics)
Risk
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TNO identifier
234176
ISSN
1079-5642
Source
Arteriosclerosis, Thrombosis, and Vascular Biology, 17 (10), 1918-1923
Document type
article