THE 5A 6A POLYMORPHISM IN THE PROMOTER OF THE STROMELYSIN-1 (MMP-3) GENE PREDICTS PROGRESSION OF ANGIOGRAPHICALLY DETERMINED CORONARY-ARTERY DISEASE IN MEN IN THE LOCAT GEMFIBROZIL STUDY/
Se. Humphries et al., THE 5A 6A POLYMORPHISM IN THE PROMOTER OF THE STROMELYSIN-1 (MMP-3) GENE PREDICTS PROGRESSION OF ANGIOGRAPHICALLY DETERMINED CORONARY-ARTERY DISEASE IN MEN IN THE LOCAT GEMFIBROZIL STUDY/, Atherosclerosis (Amsterdam), 139(1), 1998, pp. 49-56
The relationship between the 5A/6A stromelysin-1 promoter polymorphism
and progression of angiographically determined coronary artery diseas
e (CAD) has been examined in men treated for 32 months with gemfibrozi
l or placebo in the Lopid Coronary Angiography Trial (LOCAT). The freq
uency of the 5A allele was 0.40 (95% CI, 0.36-0.43), and in the sample
as a whole 12% of the men were homozygous for the 5A allele. In the p
lacebo group, diffuse progression of disease was, on average, complete
ly prevented in men with the genotype 5A/5A as measured by a 0.30% inc
rease in mean average diameter of the coronary artery segments (ADS),
compared with a mean 1.79% decrease in the combined group with the gen
otype 5A6A or 6A6A (mean +/- S.E.M., +0.007 +/- 0.020 mm vs. -0.043 +/
- 0.0.08 mm, P = 0.03). A similar relationship with genotype was seen
for disease progression determined by the mean minimal luminal diamete
r (MLD); with the 5A5A group decreasing by an average of 1.72% compare
d with 5.54% in the 5A/6A plus 6A/6A group (-0.029 +/- 0.034 mm vs. -0
.102 +/- 0.013 mm, P = 0.06). In the gemfibrozil-treated group, the ef
fect on disease progression associated with the 5A/6A alleles was of a
similar pattern as in the placebo group, but the effect was less mark
ed and was not statistically significant. This study confirms the prev
iously reported beneficial effect on disease progression associated wi
th the 5A allele and raises the possibility that patients with CAD who
are homozygous for the 6A allele, and who represent 25-30% of the pop
ulation, may be at particular risk of rapid progression of disease and
may require particularly aggressive lipid lowering therapy to prevent
disease progression. (C) 1998 Elsevier Science Ireland Ltd. All right
s reserved.