Impact of 12-SNP and 6-SNP Polygenic Scores on Predisposition to High LDL-Cholesterol Levels in Patients with Familial Hypercholesterolemia.
Genes (Basel)
; 15(4)2024 04 06.
Article
em En
| MEDLINE
| ID: mdl-38674396
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Predisposição Genética para Doença
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Herança Multifatorial
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Polimorfismo de Nucleotídeo Único
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Hiperlipoproteinemia Tipo II
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LDL-Colesterol
Limite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Genes (Basel)
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Itália