Relation between single nucleotide polymorphisms in circadian clock relevant genes and cholesterol metabolism

Single nucleotide polymorphisms (SNPs) in circadian clock relevant genes are associated with several metabolic health variables, but little is known about their associations with human cholesterol metabolism. Therefore, this study examined associations between SNPs in ARNTL, ARNTL2, CLOCK, CRY], CRY2, PER2, and PER3 with the intes-tinal cholesterol absorption markers campesterol and sitosterol, the endogenous cholesterol synthesis marker lathosterol, and total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) concentrations in 456 healthy individuals from Western European descent. One SNP in ARNTL2 (rs1037924) showed a significant asso-ciation with lathosterol. Several SNPs in ARNTL (rs4146388, rs58901760, rs6486121), ARNTL2 (rs73075788), CLOCK (rs13113518, rs35115774, rs6832769), and CRY] (rs2078074) were significantly associated with intesti-nal cholesterol absorption. Genetic variants in CRY2, PER2, and PER3 were not significantly associated with intes-tinal cholesterol absorption or endogenous cholesterol synthesis. None of the SNPs were associated with TC or LDL-C, except for one SNP in PER2 (rs11894491) with serum LDL-C concentrations. The findings suggest that var-ious SNPs in ARNTL, ARNTL2, CLOCK and CRY] play a role in intestinal cholesterol absorption and endogenous cho-lesterol synthesis, which was not reflected in TC and LDL-C concentrations. The significant associations between SNPs and intestinal cholesterol absorption and endogenous cholesterol synthesis should be validated in other co-horts. (c) 2023 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).