| Title: | Evaluation of plasma apolipoproteins in heterozygous carriers of ABCG5/8 mutations |
| Journal: | European Journal of Medical Research |
| Published: | 3 Aug 2026 |
| DOI: | https://doi.org/10.1186/s40001-026-04976-8 |
Publication 21226
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Abstract
BackgroundSitosterolemia is an autosomal recessive disorder caused by mutations in ABCG5/8. Previous studies have reported that heterozygous carriers of ABCG5/8 mutations (Sito_het) are at an increased risk of coronary heart disease. Given the established role of apolipoproteins in lipid-related disorders, this study aimed to characterize the biological alterations in Sito_het and to explore diagnostic models to identify Sito_het individuals based on plasma apolipoprotein profiles.MethodsTwo datasets were analyzed: Dataset 1 comprised 14 Sito_het, 16 hyperlipidemia (HC) and 96 healthy (Con) individuals, with 12 apolipoproteins and Lp(a) quantified by liquid chromatography mass spectrometry. Dataset 2 included 1121 Sito_het participants from the UK Biobank, with ABCG5/8 genotypes from whole exome sequencing and apolipoprotein levels from Olink proteomics. Selected apolipoproteins identified in Dataset 1 were then independently validated in Dataset 2.ResultsTwo nomogram models were developed using multivariable logistic regression: the first incorporated ApoB, ApoM, and ApoC2 for discriminating Sito_het from Controls, and the second incorporated ApoC2 and Lp(a) for discriminating Sito_het from HC patients. Both models demonstrated good performance with respect to calibration, precision-recall, receiver-operating characteristic analysis, decision curve analysis, and clinical impact assessment. External validation using the UK Biobank cohort confirmed the differences in plasma levels of shared apolipoproteins among the Sito_het, Con, and HC groups.ConclusionThe nomogram models demonstrated promising discriminative performance in distinguishing Sito_het from both HC and healthy controls in this retrospective derivation cohort. Although these findings are exploratory and require further prospective evaluation in larger, independent cohorts, our work provides a useful analytical framework for future research related to ABCG5/8 heterozygous carriers.</p>
7 Authors
- Shijie Xu
- Jun Zhang
- Lei Xiao
- Jialu Li
- Luya Wang
- Yan Chen
- Junfang Wu
1 Application
| Application ID | Title |
|---|---|
| 95608 | The associations between genetic background, different exposures and cardiovascular diseases |
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