We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Impact of 12-SNP and 6-SNP Polygenic Scores on Predisposition to High LDL-Cholesterol Levels in Patients with Familial Hypercholesterolemia.
- Authors
Cardiero, Giovanna; Ferrandino, Martina; Calcaterra, Ilenia Lorenza; Iannuzzo, Gabriella; Di Minno, Matteo Nicola Dario; Buganza, Raffaele; Guardamagna, Ornella; Auricchio, Renata; Di Taranto, Maria Donata; Fortunato, Giuliana
- Abstract
Background: Familial hypercholesterolemia (FH) comprises high LDL-cholesterol (LDL-c) levels and high cardiovascular disease risk. In the absence of pathogenic variants in causative genes, a polygenic basis was hypothesized. Methods: In a population of 418 patients (excluding homozygotes) with clinical suspicion of FH, the FH-causative genes and the regions of single nucleotide polymorphisms (SNPs) included in 12-SNP and 6-SNP scores were sequenced by next-generation sequencing, allowing for the detection of pathogenic variants (V+) in 220 patients. To make a comparison, only patients without uncertain significance variants (V−/USV−) were considered (n = 162). Results: Higher values of both scores were observed in V+ than in V−. Considering a cut-off leading to 80% of V−/USV− as score-positive, a lower prevalence of patients positive for both 12-SNP and 6-SNP scores was observed in V+ (p = 0.010 and 0.033, respectively). Mainly for the 12-SNP score, among V+ patients, higher LDL-c levels were observed in score-positive (223 mg/dL -IQR 187-279) than in negative patients (212 mg/dL -IQR 162–240; p = 0.006). Multivariate analysis confirmed the association of scores and LDL-c levels independently of age, sex, and presence of pathogenic variants and revealed a greater association in children. Conclusions: The 12-SNP and 6-SNP polygenic scores could explain hypercholesterolemia in patients without pathogenic variants as well as the variability of LDL-c levels among patients with FH-causative variants.
- Subjects
FAMILIAL hypercholesterolemia; LDL cholesterol; SINGLE nucleotide polymorphisms; NUCLEOTIDE sequencing
- Publication
Genes, 2024, Vol 15, Issue 4, p462
- ISSN
2073-4425
- Publication type
Article
- DOI
10.3390/genes15040462