Comparison of two polygenic risk scores to identify non-monogenic primary hypocholesterolemias in a large cohort of Italian hypocholesterolemic subjects
| Autor: | Angelo B. Cefalù, Rossella Spina, Davide Noto, Claudio Rabacchi, Antonina Giammanco, Maria Luisa Simone, Federica Brucato, Chiara Scrimali, Maria Grazia Gueli-Alletti, Carlo M. Barbagallo, Patrizia Tarugi, Maurizio R. Averna |
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| Rok vydání: | 2022 |
| Předmět: |
Multifactorial Inheritance
Nutrition and Dietetics Endocrinology Diabetes and Metabolism Lipid Metabolism Disorders Cholesterol LDL Hypobetalipoproteinemia Mutations Polygenic risk score Panel based NGS sequencing Hypobetalipoproteinemias Polygenic risk score Risk Factors Panel based NGS sequencing Mutation Internal Medicine Humans Proprotein Convertase 9 Cardiology and Cardiovascular Medicine Hypobetalipoproteinemia Mutations Angiopoietin-Like Protein 3 Apolipoproteins B Monomeric GTP-Binding Proteins |
| Zdroj: | Journal of clinical lipidology. 16(4) |
| ISSN: | 1933-2874 |
| Popis: | Primary Hypobetalipoproteinemias (HBL) are a group of dominant and recessive monogenic genetic disorders caused by mutations in APOB, PCSK9, ANGPTL3, MTTP, Sar1b genes and characterized by plasma levels of total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C) and apolipoprotein B (apoB) below the 5To explore the complex genetic architecture of HBL we compared two polygenic risk scores in order to assess the role of the polygenic burden and the differences in the clinical phenotype between monogenic and polygenic HBL; we studied a cohort of 170 subjects with primary HBL referred over a 25-year period to 2 Italian reference centers have been studied.The genetic analyses have been based on: Sanger sequencing, in-house NGS customized panel and two scores, PRS1 and PRS2 for the polygenic burden.Sixty 60 (35%) and 63 (37%) subjects had a monogenic and polygenic HBL respectively. LDL-C plasma levels were significantly lower in monogenic HBL (30.87 ± 3.12 mg/dl) compared with the non-monogenic HBL (42.80 ± 2.18 mg/dl) (p0.002) with no differences in the percentage of fatty liver.Only PRS1 is effective in detecting polygenic HBL while PRS2 does not improve the polygenic diagnosis. |
| Databáze: | OpenAIRE |
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