BACKGROUND: The Azorean population presents the highest standardized mortality 
rate for cardiovascular diseases (CVD) when compared to mainland Portugal and 
other populations. Since thrombosis is a common cause of CVD, we assessed four 
polymorphisms in three thrombotic risk genes - F5 (G1691A), F2 (G20210A) and 
MTHFR (C677T, A1298C), in 469 healthy blood donors from São Miguel Island 
(Azores). We also analysed the CYP2C9 (C430T, A1075C) and VKORC1 (G1639A) 
variants in fifty-eight individuals with predisposition to thrombosis 
(possessing at least one variation in F5 or F2 genes and one in MTHFR) to 
evaluate their warfarin drug response genetic profiles.
RESULTS: Among the 469 individuals, the data showed that thrombotic risk allele 
frequencies - 1691A (4.9%), 20210A (1.8%), 677T (41.7%) and 1298C (24.8%) - were 
similar to other Caucasians, but significantly different from mainland 
Portuguese (chi2, p < 0.001). The combined analysis of these variants identified 
twenty-two different genetic profiles (genotype order: F5, F2, MTHFR C677T and 
A1298C). Complete homozygosity for all wild-type alleles (GG GG CC AA) was 
present in 11.7%, being GG GG CT AA (22.4%) the most frequent profile. The 
results also demonstrated that 12.4% (58 out of 469) of São Miguel islanders 
have increased genetic predisposition to thrombosis. Subsequently, we evaluated 
these individuals for their warfarin response genetic profiles. The data showed 
that seven out of fifty-eight individuals are poor metabolizers (two with 
CYP2C9*2/*2 and five with CYP2C9*2/*3 genotypes). VKORC1 polymorphism analysis 
identified twelve individuals (20.7%) with AA genotype, who probably will 
require lower doses of warfarin. The joint analysis of CYP2C9 and VKORC1 
revealed that 79.3% (46 out of 58) of the individuals carry at least one 
polymorphism in these genes. Within these, twenty-five individuals (43.1%) need 
intermediate and/or low doses of warfarin, if treatment is started.
CONCLUSION: The present study demonstrated, for the first time, that São Miguel, 
and possibly the Azores population, shows significant differences on allele 
frequencies of thrombotic risk factors when compared to mainland Portugal. This 
research constitutes a primary approach for future studies on CVD, as well as 
for the implementation of warfarin dosing protocols using the patient's 
genotypic information.