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

被引:2
|
作者
Satny, Martin [1 ,10 ]
Todorovova, Veronika [1 ]
Altschmiedova, Tereza [1 ]
Hubacek, Jaroslav A. [1 ,2 ]
Dlouha, Lucie [3 ]
Lanska, Vera [2 ]
Soska, Vladimir [4 ,5 ,6 ]
Kyselak, Ondrej [4 ,5 ,6 ]
Freiberger, Tomas [7 ,8 ]
Bobak, Martin [8 ,9 ]
Vrablik, Michal [1 ]
机构
[1] Charles Univ Prague, Gen Univ Hosp, Fac Med 1, Dept Internal Med 3, Prague, Czech Republic
[2] Inst Clin & Expt Med, Ctr Expt Med, Prague, Czech Republic
[3] Charles Univ Prague, Fac Sci, Dept Anthropol & Human Genet, Prague, Czech Republic
[4] St Anne Univ Hosp, Clin Biochem Dept, Brno, Czech Republic
[5] Masaryk Univ, Internal Dept 2, Fac Med, Brno, Czech Republic
[6] St Anne Univ Hosp, Brno, Czech Republic
[7] Ctr Cardiovasc Surg & Transplantat, Brno, Czech Republic
[8] Masaryk Univ, Med Fac, Brno, Czech Republic
[9] UCL, Inst Epidemiol & Hlth Care, London WC1E 7HB, England
[10] Charles Univ Prague, Gen Univ Hosp Prague, Fac Med 1, Dept Internal Med 3, U Nemocnice 1, Prague 2, Czech Republic
关键词
Familial dysbetalipoproteinemia; Cardiovascular risk; Polymorphism; Genetic risk score; III HYPERLIPOPROTEINEMIA; APOLIPOPROTEIN-E; POPULATION; DIAGNOSIS; DISEASE; LOCI; TRIGLYCERIDE; COMMON;
D O I
10.1016/j.jacl.2023.11.010
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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. (c) 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/ )
引用
收藏
页码:e230 / e237
页数:8
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