Genetic risk score in patients with the APOE2/E2 genotype as a predictor of familial dysbetalipoproteinemia
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
38044203
DOI
10.1016/j.jacl.2023.11.010
PII: S1933-2874(23)00342-2
Knihovny.cz E-resources
- Keywords
- Cardiovascular risk, Familial dysbetalipoproteinemia, Genetic risk score, Polymorphism,
- MeSH
- Apolipoprotein E2 * genetics MeSH
- Adult MeSH
- Genetic Risk Score MeSH
- Genotype MeSH
- Hyperlipoproteinemia Type III * genetics MeSH
- Polymorphism, Single Nucleotide MeSH
- Middle Aged MeSH
- Humans MeSH
- Aged MeSH
- Case-Control Studies MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Apolipoprotein E2 * MeSH
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.
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