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CETP variants rs2033254 and rs12708980 associate with lower intestinal cholesterol absorption markers in a European GWAS (Nutrients 2026)
Original title: Genome-Wide Association of Genetic Variants with Intestinal Cholesterol Absorption Markers in a European Population
This genome-wide association study in 398 healthy Europeans identified two single-nucleotide polymorphisms in CETP (rs2033254 and rs12708980) associated with lower total cholesterol-standardized campesterol and sitosterol levels. The analysis evaluated 166,037 common genetic variants and found 16 associated SNPs, with two reaching genome-wide significance across both absorption markers. These findings position CETP as a genetic determinant of intestinal cholesterol absorption, though the modest sample size and lack of functional validation require independent replication before clinical translation.
Original abstract
Background: Interindividual variability in intestinal cholesterol absorption contributes to differences in serum lipid concentrations and cardiovascular risk. Total cholesterol (TC)-standardized campesterol and sitosterol levels are established markers of cholesterol absorption. However, genetic variants in Europeans associated with these markers remain incompletely characterized. Methods: A genome-wide association study (GWAS) was performed in 398 healthy individuals of European ancestry. Samples were genotyped using the Precision Medicine Research Array (PMRA). After quality control, 166,037 common genetic variants with a minor allele frequency (MAF) > 20% were analyzed. Associations between genetic variants and intestinal cholesterol absorption markers (campesterol/TC and sitosterol/TC) were evaluated using additive and recessive genetic models. Results: A total of 16 SNPs were identified. Eight SNPs overlapped with both campesterol/TC and sitosterol/TC, of which 2 reached genome-wide significance. Six overlapping SNPs were associated with higher concentrations of both markers: 3 SNPs in ABCG8 (rs4299376, rs6544713, and rs4245791), 1 SNP in ADAM12 (rs4962526), and 2 SNPs in non-coding regions (rs260769 and rs5011112). Additionally, two SNPs (rs2033254 and rs12708980) in CETP were associated with lower concentrations of these markers. Five of the identified SNPs have not previously been linked to markers of intestinal cholesterol absorption. Conclusions: This GWAS confirmed previously reported associations within ABCG8 and identified candidate loci in CETP and ADAM12 that may be involved in intestinal cholesterol absorption. These findings contribute to our understanding of genetic factors underlying intestinal cholesterol absorption and highlight candidate loci for future replication and functional studies.
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Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 28 August 2026. Methods.