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Single nucleotide polymorphisms (SNPs) have been associated with cholesterol metabolism and may partly explain large inter-individual variability in intestinal cholesterol absorption and endogenous cholesterol synthesis rates. This cross-sectional study therefore examined whether SNPs in genes encoding for proteins involved in intestinal cholesterol absorption ( ABCG5, ABCG8, and NPC1L1 ) and endogenous cholesterol synthesis ( CYP51A1 , DHCR7 , DHCR24 , HMGCR , HSD17B7 , LBR, and MSMO1 ) were associated with intestinal cholesterol absorption markers (total cholesterol (TC) standardized campesterol and sitosterol levels), an endogenous cholesterol synthesis marker (TC-standardized lathosterol levels), and serum low-density lipoprotein cholesterol (LDL-C) concentrations in a European cohort. ABCG5 (rs4245786) and the tag SNP ABCG8 (rs4245791) were significantly associated with serum campesterol and/or sitosterol levels. In contrast, NPC1L1 (rs217429 and rs217416) were significantly associated with serum lathosterol levels. The tag SNP in HMGCR (rs12916) and a SNP in LBR (rs12141732) were significantly associated with serum LDL-C concentrations. SNPs in the cholesterol absorption genes were not associated with serum LDL-C concentrations. SNPs in CYP51A1, DHCR24, HSD17B7, and MSMO1 were not associated with the serum non-cholesterol sterols and LDL-C concentrations. Given the variable efficiency of cholesterol-lowering interventions, the identification of SNPs associated with cholesterol metabolism could be a step forward towards personalized approaches.

Associations between SNPs in Intestinal Cholesterol Absorption and Endogenous Cholesterol Synthesis Genes with Cholesterol Metabolism