Abstract
Currently, the established risk factors for cardiovascular disease (CVD) are largely
environmental in nature. Conflicting studies have suggested that mutations in specific
coagulation genes may also provide a genetic basis for CVD risk. We reviewed clinical
studies that examined the role of single nucleotide polymorphisms in coagulation and
platelet factors, and a biochemical factor to determine if specific genotypes are
correlated with patients with a history of arterial thrombotic diseases (acute coronary
syndromes or stroke). A meta-analysis was performed on studies for factors II (G20210A
variant), V Leiden (G1691A), VII (R353Q), glycoprotein (GP) IIIa receptor (PIA1/A2), and methylenetetrahydrofolate reductase (MTHFR, C677T). There was no correlation
for factor II or factor V polymorphisms to coronary artery disease (CAD) in 5,607
and 5,431 patients studied, respectively. There was also no correlation for factor
II variants and stroke in 3,451 patients studied. For factor V, statistical significance
was achieved for the G1691A variant on 3,399 patients with stroke (odds ratio [OR]
1.43, 95% confidence intervals [CI] 1.03 to 1.97). The GP IIIa PIA1/A2 genotype was associated with increased risk for CAD in 7,920 patients (OR 1.12, 95%
CI 1.01 to 1.24), but not for 1,855 patients who had a stroke (OR 0.80, 95% CI 0.62
to 1.04). The combined RQ and RR genotypes of factor VII R353Q were correlated to
a reduced risk for CVD in 2,574 patients (OR 0.78, 95% CI 0.65 to 0.93), whereas the
QQ genotype had offered more protection (OR 0.53, 95% CI 0.27 to 1.03). The TT homozygous
variant of MTHFR was associated with CAD risk in 5,644 patients studied (OR 1.30,
95% CI 1.11 to 1.52) but not for 3,075 patients with stroke. This study shows that
for some genes, further studies are unnecessary, whereas for others, no more enrollments
are needed. The impact of certain genotypes must be examined in relation to other
established risk factors and potentially new therapeutic strategies.
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Article info
Publication history
Accepted:
January 9,
2001
Received in revised form:
January 9,
2001
Received:
November 14,
2000
Identification
Copyright
© 2001 Excerpta Medica Inc. Published by Elsevier Inc. All rights reserved.
