TY - JOUR
T1 - Genetic variation in the rate-limiting enzyme in cholesterol catabolism (cholesterol 7alpha-hydroxylase) influences the progression of atherosclerosis and risk of new clinical events
AU - Hofman, Maaike K.
AU - Princen, Hans M. G.
AU - Zwinderman, Aeilko H.
AU - Jukema, J. Wouter
PY - 2005
Y1 - 2005
N2 - CHD (coronary heart disease) is a complex disorder which is, in part, related to serum cholesterol levels. The rate-limiting enzyme in the catabolism of cholesterol into bile acids is CYP7A1 (cholesterol 7alpha-hydroxylase). The effect of the CYP7A1 A-278C promoter polymorphism on the progression of atherosclerosis, risk of a new clinical event and the influence of this variant on cholesterol-lowering therapy was investigated in 715 male patients with coronary atherosclerosis participating in REGRESS (Regression Growth Evaluation Statin Study). Genotype distributions were as follows: 283 with AA; 330 with AC and 102 with CC. There were no significant differences in baseline characteristics and serum lipids between genotypes. After 2 years, CC carriers had more progression of diffuse and focal atherosclerosis compared with AA carriers, as indicated by a larger decrease in MSD (mean segment diameter; 0.09 mm compared with 0.06 mm respectively; P=0.009) and MOD (minimum obstruction diameter; 0.09 mm compared with 0.05 mm respectively; P=0.024). Inclusion of risk factors for CHD in the model showed the same trend, although not significant for MOD (P=0.01 for MSD, and P=0.06 for MOD). In addition, CC carriers had an almost 2-fold higher risk of a new clinical event compared with AA carriers [RR (95% CI) 1.93 (1.11-3.36); P=0.02; where RR is relative risk and CI is confidence interval]. Inclusion of risk factors for CHD in the model showed the same trend, although not significant [RR (95% CI), 1.74 (0.96-3.12); P=0.06]. In conclusion, we present evidence that the CC variant of the A-278C polymorphism in the rate-limiting enzyme in the catabolism of cholesterol, CYP7A1, increases the progression of atherosclerosis and possibly the risk of a new clinical event
AB - CHD (coronary heart disease) is a complex disorder which is, in part, related to serum cholesterol levels. The rate-limiting enzyme in the catabolism of cholesterol into bile acids is CYP7A1 (cholesterol 7alpha-hydroxylase). The effect of the CYP7A1 A-278C promoter polymorphism on the progression of atherosclerosis, risk of a new clinical event and the influence of this variant on cholesterol-lowering therapy was investigated in 715 male patients with coronary atherosclerosis participating in REGRESS (Regression Growth Evaluation Statin Study). Genotype distributions were as follows: 283 with AA; 330 with AC and 102 with CC. There were no significant differences in baseline characteristics and serum lipids between genotypes. After 2 years, CC carriers had more progression of diffuse and focal atherosclerosis compared with AA carriers, as indicated by a larger decrease in MSD (mean segment diameter; 0.09 mm compared with 0.06 mm respectively; P=0.009) and MOD (minimum obstruction diameter; 0.09 mm compared with 0.05 mm respectively; P=0.024). Inclusion of risk factors for CHD in the model showed the same trend, although not significant for MOD (P=0.01 for MSD, and P=0.06 for MOD). In addition, CC carriers had an almost 2-fold higher risk of a new clinical event compared with AA carriers [RR (95% CI) 1.93 (1.11-3.36); P=0.02; where RR is relative risk and CI is confidence interval]. Inclusion of risk factors for CHD in the model showed the same trend, although not significant [RR (95% CI), 1.74 (0.96-3.12); P=0.06]. In conclusion, we present evidence that the CC variant of the A-278C polymorphism in the rate-limiting enzyme in the catabolism of cholesterol, CYP7A1, increases the progression of atherosclerosis and possibly the risk of a new clinical event
U2 - https://doi.org/10.1042/CS20040339
DO - https://doi.org/10.1042/CS20040339
M3 - Article
C2 - 15707388
SN - 0143-5221
VL - 108
SP - 539
EP - 545
JO - Clinical science (London, England
JF - Clinical science (London, England
IS - 6
ER -