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

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 b ile 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 pla sma LDL-cholesterol concentrations but the effect of this polymorphism is u nknown in the general population, The aim of the present study was therefor e to investigate the association of this polymorphism to lipoprotein levels in a population-based sample of 1139 male and 1191 female Framingham Offsp ring participants, In men, the C variant was associated with higher plasma concentrations of LDL- cholesterol and this association remained significan t after adjustment for familial relationship, age, BMI, smoking, alcohol in take, the use of beta-blockers, and apoE genotype, The C variant was also a ssociated with an increased TC/ HDL ratio in men, Variance components analy sis indicated that allelic variability at nucleotide -204 of the CYP7 gem a nd polymorphism of the apoE gene accounted for 1 and 5% of the variation of plasma LDL-cholesterol concentrations, respectively, In women, however, th ere was no relationship between LDL-cholesterol and the A-204C polymorphism but subjects homozygous for the CC genotype had significantly lower trigly ceride 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.jlr Thus, our results show that the A-204C polymorphism in the CYP7 gem is associated with stati stically significant variations in LDL-C and triglyceride concentrations in men and women, respectively, but the cumulative effects of these variation s on atherosclerotic risk remain uncertain.