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 7α-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.
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Research Article|
May 24 2005
Genetic variation in the rate-limiting enzyme in cholesterol catabolism (cholesterol 7α-hydroxylase) influences the progression of atherosclerosis and risk of new clinical events
Maaike K. HOFMAN;
Maaike K. HOFMAN
*TNO Prevention and Health, Gaubius Laboratory, Leiden, The Netherlands
†Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands
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Hans M. G. PRINCEN;
Hans M. G. PRINCEN
*TNO Prevention and Health, Gaubius Laboratory, Leiden, The Netherlands
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Aeilko H. ZWINDERMAN;
Aeilko H. ZWINDERMAN
‡Department of Clinical Epidemiology and Biostatistics, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
§Interuniversity Cardiology Institute of The Netherlands, Utrecht, The Netherlands
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J. Wouter JUKEMA
§Interuniversity Cardiology Institute of The Netherlands, Utrecht, The Netherlands
∥Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands
Correspondence: Dr J. Wouter Jukema, Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands (email [email protected]).
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Publisher: Portland Press Ltd
Received:
November 29 2004
Revision Received:
February 04 2005
Accepted:
February 11 2005
Accepted Manuscript online:
February 11 2005
Online ISSN: 1470-8736
Print ISSN: 0143-5221
The Biochemical Society
2005
Clin Sci (Lond) (2005) 108 (6): 539–545.
Article history
Received:
November 29 2004
Revision Received:
February 04 2005
Accepted:
February 11 2005
Accepted Manuscript online:
February 11 2005
Citation
Maaike K. HOFMAN, Hans M. G. PRINCEN, Aeilko H. ZWINDERMAN, J. Wouter JUKEMA; Genetic variation in the rate-limiting enzyme in cholesterol catabolism (cholesterol 7α-hydroxylase) influences the progression of atherosclerosis and risk of new clinical events. Clin Sci (Lond) 1 June 2005; 108 (6): 539–545. doi: https://doi.org/10.1042/CS20040339
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