Satny, M;
Todorovova, V;
Altschmiedova, T;
Hubacek, JA;
Dlouha, L;
Lanska, V;
Soska, V;
... Vrablik, M; + view all
(2024)
Genetic risk score in patients with the APOE2/E2 genotype as a predictor of familial dysbetalipoproteinemia.
Journal of Clinical Lipidology
, 18
(2)
e230-e237.
10.1016/j.jacl.2023.11.010.
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Abstract
BACKGROUND: Familial dysbetalipoproteinemia (FD) is an autosomal recessive (rarely dominant) inherited disorder that is almost exclusively associated with the apolipoprotein E gene (APOE) variability. Nonetheless, only a small proportion of APOE2/E2 subjects develop the phenotype for mixed dyslipidemia; the context of other trigger metabolic or genetic factors remains unknown. METHODS: One hundred and one patients with FD and eighty controls (all APOE2/E2 homozygotes; rs429358) were screened for 18 single-nucleotide polymorphisms (SNPs) within the genes involved in triglyceride metabolism. RESULTS: Two SNPs were significantly associated with the FD phenotype (rs439401 within APOE; P < 0.0005 and rs964184 within ZPR1/APOA5/A4/C3/A1 gene cluster; P < 0.0001). Unweighted genetic risk scores - from these two SNPs (GRS2), and, also, additional 13 SNPs with P-value below 0.9 (GRS15) - were created as an additional tool to improve the risk estimation of FD development in subjects with the APOE2/E2 genotype. Both GRS2 and GRS15 were significantly (P < 0.0001) increased in patients and both GRSs discriminated almost identically between the groups (P = 0.86). Subjects with an unweighted GRS2 of three or more had an almost four-fold higher risk of FD development than other individuals (odds ratio (OR) 3.58, 95% confidence interva (CI): 1.78–7.18, P < 0.0005). CONCLUSIONS: We identified several SNPs that are individual additive factors influencing FD development. The use of unweighted GRS2 is a simple and clinically relevant tool that further improves the prediction of FD in APOE2/E2 homozygotes with corresponding biochemical characteristics.
| Type: | Article |
|---|---|
| Title: | Genetic risk score in patients with the APOE2/E2 genotype as a predictor of familial dysbetalipoproteinemia |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.jacl.2023.11.010 |
| Publisher version: | https://doi.org/10.1016/j.jacl.2023.11.010 |
| Language: | English |
| Additional information: | © 2024 The Authors. Published by Elsevier Inc. on behalf of National Lipid Association. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) |
| Keywords: | Familial dysbetalipoproteinemia; Cardiovascular risk; Polymorphism; Genetic risk score |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Epidemiology and Health > Epidemiology and Public Health |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10211024 |
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