Background and aim
Considerable variation in cholesterol metabolism and responses to lipid-lowering treatment exists between individuals. This may partly be explained by single-nucleotide polymorphisms (SNPs) in genes that are essential in cholesterol metabolism. Therefore, we aimed to study associations between SNPs in genes involved in cholesterol metabolism with intestinal cholesterol absorption, endogenous cholesterol synthesis, and  serum low-density lipoprotein cholesterol (LDL-C) concentrations in a European cohort. 

Methods
Various SNPs were selected in three intestinal cholesterol absorption genes (ABCG5, ABCG8, and NPC1L1) and seven endogenous cholesterol synthesis genes (CYP51A1, DHCR7, DHCR24, HMGCR, HSD17B7, LBR, and MSMO1). The associations between SNPs in these genes with two intestinal cholesterol absorption markers (total cholesterol-standardized sitosterol and campesterol), an endogenous cholesterol synthesis marker (total cholesterol-standardized lathosterol), and serum LDL-C concentrations were studied in 456 European individuals.

Results
Significant associations were found for ABCG5 (rs4245786) and ABCG8 (rs4245791) with serum intestinal cholesterol markers. Furthermore, NPC1L1 (rs217416 and rs217429) were significantly associated with serum lathosterol levels. SNPs in CYP51A1, DHCR24, HMGCR, HSD17B7, LBR, and MSMO1 were not associated with the serum non-cholesterol sterols. In addition, none of the SNPs in cholesterol absorption and synthesis genes were associated with LDL-C concentrations, except for HMGCR (rs12916) and LBR (rs12141732).

Conclusion
Several selected SNPs in genes essential in intestinal cholesterol absorption and endogenous cholesterol synthesis showed an association with cholesterol metabolism in this European cohort. These SNPs may therefore contribute to the inter-individual variation in cholesterol metabolism.