Genetic risk score in patients with the APOE2/E2 genotype as a predictor of familial dysbetalipoproteinemia.

Autor: Satny M; 3rd Department of Internal Medicine, First Faculty of Medicine Charles University, General University Hospital, Prague, Czech Republic (Drs Satny, Todorovova, Altschmiedova, Hubacek and Vrablik). Electronic address: martin.satny@vfn.cz., Todorovova V; 3rd Department of Internal Medicine, First Faculty of Medicine Charles University, General University Hospital, Prague, Czech Republic (Drs Satny, Todorovova, Altschmiedova, Hubacek and Vrablik)., Altschmiedova T; 3rd Department of Internal Medicine, First Faculty of Medicine Charles University, General University Hospital, Prague, Czech Republic (Drs Satny, Todorovova, Altschmiedova, Hubacek and Vrablik)., Hubacek JA; 3rd Department of Internal Medicine, First Faculty of Medicine Charles University, General University Hospital, Prague, Czech Republic (Drs Satny, Todorovova, Altschmiedova, Hubacek and Vrablik); Centre of Experimental Medicine, Institute of Clinical and Experimental Medicine, Prague, Czech Republic (Drs Hubacek and Lanska)., Dlouha L; Department of Anthropology and Human Genetics, Faculty of Science, Charles University, Prague, Czech Republic (Dr Dlouha)., Lanska V; Centre of Experimental Medicine, Institute of Clinical and Experimental Medicine, Prague, Czech Republic (Drs Hubacek and Lanska)., Soska V; Clinical Biochemistry Department, St. Anne University Hospital, Brno, Czech Republic (Drs Soska and Kyselak); 2nd Internal Department, Faculty of Medicine Masaryk University and St. Anne University Hospital, Brno, Czech Republic (Drs Soska and Kyselak)., Kyselak O; Clinical Biochemistry Department, St. Anne University Hospital, Brno, Czech Republic (Drs Soska and Kyselak); 2nd Internal Department, Faculty of Medicine Masaryk University and St. Anne University Hospital, Brno, Czech Republic (Drs Soska and Kyselak)., Freiberger T; Centre for Cardiovascular Surgery and Transplantation, Brno, and Medical Faculty, Masaryk University, Brno, Czech Republic (Dr Freiberger)., Bobak M; Institute of Epidemiology and Health Care, University College London, London WC1E 7HB, United Kingdom, and Medical Faculty, Masaryk University, Brno, Czech Republic (Dr Bobak)., Vrablik M; 3rd Department of Internal Medicine, First Faculty of Medicine Charles University, General University Hospital, Prague, Czech Republic (Drs Satny, Todorovova, Altschmiedova, Hubacek and Vrablik).
Jazyk: angličtina
Zdroj: Journal of clinical lipidology [J Clin Lipidol] 2024 Mar-Apr; Vol. 18 (2), pp. e230-e237. Date of Electronic Publication: 2023 Nov 23.
DOI: 10.1016/j.jacl.2023.11.010
Abstrakt: 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.
(Copyright © 2023. Published by Elsevier Inc.)
Databáze: MEDLINE
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