Original Article

Association of the A-204C polymorphism in the cholesterol 7-hydroxylase gene with variations in plasma low density lipoprotein cholesterol levels in the Framingham Offspring Study

Correspondence to: Jose M. Ordovas

The first reaction of the catabolic pathway of cholesterol is catalyzed by CYP7 and serves as the rate-limiting step and major site of regulation of bile acid synthesis in the liver. A common A to C substitution at position -204 of the promoter of CYP7 gene has been associated with variations in plasma LDL-cholesterol concentrations but the effect of this polymorphism is unknown in the general population. The aim of the present study was therefore to investigate the association of this polymorphism to lipoprotein levels in a population-based sample of 1139 male and 1191 female Framingham Offspring participants. In men, the C variant was associated with higher plasma concentrations of LDL-cholesterol and this association remained significant after adjustment for familial relationship, age, BMI, smoking, alcohol intake, the use of beta-blockers, and apoE genotype. The C variant was also associated with an increased TC/HDL ratio in men. Variance components analysis indicated that allelic variability at nucleotide -204 of the CYP7 gene and polymorphism of the apoE gene accounted for 1 and 5% of the variation of plasma LDL-cholesterol concentrations, respectively. In women, however, there was no relationship between LDL-cholesterol and the A-204C polymorphism but subjects homozygous for the CC genotype had significantly lower triglyceride levels than heterozygotes. Moreover, no significant relationship was found between the A-204C variants and lipoprotein particle diameter or the prevalence of coronary heart disease in both genders.

Thus, our results show that the A-204C polymorphism in the CYP7 gene is associated with statistically significant variations in LDL-C and triglyceride concentrations in men and women, respectively, but the cumulative effects of these variations on atherosclerotic risk remain uncertain.—Couture, P., J. D. Otvos, L. A. Cupples, P. W. F. Wilson, E. J. Schaefer, and J. M. Ordovas. Association of the A-204C polymorphism in the cholesterol 7-hydroxylase gene with variations in plasma low density lipoprotein cholesterol levels in the Framingham Offspring Study. J. Lipid Res. 1999. 40: 1883–1889.

Supplementary key words: LDL-cholesterol, cholesterol 7-hydroxylase, genetic polymorphism

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				I. A. Pikuleva CHOLESTEROL-METABOLIZING CYTOCHROMES P450 Drug Metab. Dispos., April 1, 2006; 34(4): 513 - 520. [Abstract] [Full Text] [PDF]

				U. Hodoglugil, S. Tanyolac, D. W. Williamson, Y. Huang, and R. W. Mahley Apolipoprotein A-V: a potential modulator of plasma triglyceride levels in Turks J. Lipid Res., January 1, 2006; 47(1): 144 - 153. [Abstract] [Full Text] [PDF]

				T. Hagiwara, S. Kono, G. Yin, K. Toyomura, J. Nagano, T. Mizoue, R. Mibu, M. Tanaka, Y. Kakeji, Y. Maehara, et al. Genetic Polymorphism in Cytochrome P450 7A1 and Risk of Colorectal Cancer: The Fukuoka Colorectal Cancer Study Cancer Res., April 1, 2005; 65(7): 2979 - 2982. [Abstract] [Full Text] [PDF]

				M. D. Badzioch, R. P. Igo Jr, F. Gagnon, J. D. Brunzell, R. M. Krauss, A. G. Motulsky, E. M. Wijsman, and G. P. Jarvik Low-Density Lipoprotein Particle Size Loci in Familial Combined Hyperlipidemia: Evidence for Multiple Loci From a Genome Scan Arterioscler. Thromb. Vasc. Biol., October 1, 2004; 24(10): 1942 - 1950. [Abstract] [Full Text] [PDF]

				M. K. Hofman, R. M. Weggemans, P. L. Zock, E. G. Schouten, M. B. Katan, and H. M. G. Princen CYP7A1 A-278C Polymorphism Affects the Response of Plasma Lipids after Dietary Cholesterol or Cafestol Interventions in Humans J. Nutr., September 1, 2004; 134(9): 2200 - 2204. [Abstract] [Full Text] [PDF]

				Y. Bosse, L. Perusse, and M.-C. Vohl Genetics of LDL particle heterogeneity: from genetic epidemiology to DNA-based variations J. Lipid Res., June 1, 2004; 45(6): 1008 - 1026. [Abstract] [Full Text] [PDF]

				C. L. Welch, S. Bretschger, P.-Z. Wen, M. Mehrabian, N. Latib, J. Fruchart-Najib, J. C. Fruchart, C. Myrick, and A. J. Lusis Novel QTLs for HDL levels identified in mice by controlling for Apoa2 allelic effects: confirmation of a chromosome 6 locus in a congenic strain Physiol Genomics, March 12, 2004; 17(1): 48 - 59. [Abstract] [Full Text] [PDF]

				Y. Bosse, L. Perusse, J.-P. Despres, B. Lamarche, Y. C. Chagnon, T. Rice, D.C. Rao, C. Bouchard, and M.-C. Vohl Evidence for a Major Quantitative Trait Locus on Chromosome 17q21 Affecting Low-Density Lipoprotein Peak Particle Diameter Circulation, May 13, 2003; 107(18): 2361 - 2368. [Abstract] [Full Text] [PDF]

				S. K. Erickson, S. R. Lear, S. Deane, S. Dubrac, S. L. Huling, L. Nguyen, J. S. Bollineni, S. Shefer, H. Hyogo, D. E. Cohen, et al. Hypercholesterolemia and changes in lipid and bile acid metabolism in male and female cyp7A1-deficient mice J. Lipid Res., May 1, 2003; 44(5): 1001 - 1009. [Abstract] [Full Text] [PDF]

				A. J. Jenkins, T. J. Lyons, D. Zheng, J. D. Otvos, D. T. Lackland, D. McGee, W. T. Garvey, R. L. Klein, and The DCCT/EDIC Research Group Serum Lipoproteins in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Intervention and Complications Cohort: Associations with gender and glycemia Diabetes Care, March 1, 2003; 26(3): 810 - 818. [Abstract] [Full Text] [PDF]

				W. M. Pandak, C. Schwarz, P. B. Hylemon, D. Mallonee, K. Valerie, D. M. Heuman, R. A. Fisher, K. Redford, and Z. R. Vlahcevic Effects of CYP7A1 overexpression on cholesterol and bile acid homeostasis Am J Physiol Gastrointest Liver Physiol, October 1, 2001; 281(4): G878 - G889. [Abstract] [Full Text] [PDF]

				R. U Almario, V. Vonghavaravat, R. Wong, and S. E Kasim-Karakas Effects of walnut consumption on plasma fatty acids and lipoproteins in combined hyperlipidemia Am. J. Clinical Nutrition, July 1, 2001; 74(1): 72 - 79. [Abstract] [Full Text] [PDF]