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

Autor:	Satny, Martin, Todorovova, Veronika, Altschmiedova, Tereza, Hubacek, Jaroslav A., Dlouha, Lucie, Lanska, Vera, Soska, Vladimir, Kyselak, Ondrej, Freiberger, Tomas, Bobak, Martin, Vrablik, Michal
Předmět:	RISK assessment HYPERLIPOPROTEINEMIA DESCRIPTIVE statistics GENETIC risk score ODDS ratio APOLIPOPROTEINS CASE-control method TRIGLYCERIDES CONFIDENCE intervals DISEASE susceptibility GENOTYPES SINGLE nucleotide polymorphisms PHENOTYPES DISEASE risk factors
Zdroj:	Journal of Clinical Lipidology; Mar2024, Vol. 18 Issue 2, pe230-e237, 8p
Abstrakt:	• 5 % of APOE2/E2 homozygotes develop familial dysbetalipoproteinemia (FD). • several gene SNPs are individual additive factors influencing FD development. • unweighted GRS2 is a clinically relevant tool that improves the prediction of FD. 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. 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. 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). 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. [ABSTRACT FROM AUTHOR]
Databáze:	Supplemental Index
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