Author, as appears in the article.: Martín-Campos JM; Ruiz-Nogales S; Ibarretxe D; Ortega E; Sánchez-Pujol E; Royuela-Juncadella M; Vila À; Guerrero C; Zamora A; Soler i Ferrer C; Arroyo JA; Carreras G; Martínez-Figueroa S; Roig R; Plana N; Blanco-Vaca F

Department: Medicina i Cirurgia

URV's Author/s: Ibarretxe Gerediaga, Daiana / Plana Gil, Núria

Keywords: Risk score Prevalence Molecular diagnosis Loci Lipid-levels Genetic risk scores Familial hypercholesterolemia Cholesterol gene score Children Care Cardiovascular-disease Cardiovascular risk Atherosclerosis

Abstract: © 2020 by the authors. Familial hypercholesterolemia (FH) is associatedwithmutations in the low-density lipoprotein (LDL) receptor (LDLR), apolipoprotein B (APOB), and proprotein convertase subtilisin/kexin 9 (PCSK9) genes. A pathological variant has not been identified in 30-70% of clinically diagnosed FH patients, and a burden of LDL cholesterol (LDL-c)-raising alleles has been hypothesized as a potential cause of hypercholesterolemia in these patients. Our aim was to study the distribution of weighted LDL-c-raising single-nucleotide polymorphism(SNP) scores (weighted gene scores orwGS) in a population recruited in a clinical setting in Catalonia. The study included 670 consecutive patients with a clinical diagnosis of FH and a prior genetic study involving 250 mutation-positive (FH/M+) and 420 mutation-negative (FH/M) patients. Three wGSs based on LDL-c-raising variants were calculated to evaluate their distribution among FH patients and compared with 503 European samples from the 1000 Genomes Project. The FH/M patients had significantly higher wGSs than the FH/M+ and control populations, with sensitivities ranging from 42% to 47%. A wGS based only on the SNPs significantly associated with FH (wGS8) showed a higher area under the receiver operating characteristic curve, and higher diagnostic specificity and sensitivity, with 46.4% of the subjects in the top quartile. wGS8 would allow for the assignment of a genetic cause to 66.4% of the patients if those with polygenic FH are added to the 37.3% of patients with monogenic FH. Our data indicate that a score based on 8 SNPs and the75th percentile cutoff point may identify patients with polygenic FH in Catalonia, although with limited diagnostic sensitivity and specificity.

Thematic Areas: Pharmacology & pharmacy Medicine, research & experimental Medicine (miscellaneous) General biochemistry,genetics and molecular biology Ciencias sociales Biochemistry, genetics and molecular biology (miscellaneous) Biochemistry, genetics and molecular biology (all) Biochemistry & molecular biology

licence for use: https://creativecommons.org/licenses/by/3.0/es/

Author's mail: daiana.ibarretxe@urv.cat nuria.plana@urv.cat

Author identifier: 0000-0002-4231-7618

Record's date: 2023-02-26

Papper version: info:eu-repo/semantics/publishedVersion

Link to the original source: https://www.mdpi.com/2227-9059/8/9/353

Licence document URL: http://repositori.urv.cat/ca/proteccio-de-dades/

Papper original source: Biomedicines. 8 (9):

APA: Martín-Campos JM; Ruiz-Nogales S; Ibarretxe D; Ortega E; Sánchez-Pujol E; Royuela-Juncadella M; Vila À; Guerrero C; Zamora A; Soler i Ferrer C; Arroyo (2020). Polygenic markers in patients diagnosed of autosomal dominant hypercholesterolemia in Catalonia: Distribution of weighted LDL-c-raising SNP scores and refinement of variant selection. Biomedicines, 8(9), -. DOI: 10.3390/BIOMEDICINES8090353

Article's DOI: 10.3390/BIOMEDICINES8090353

Entity: Universitat Rovira i Virgili

Journal publication year: 2020

Publication Type: Journal Publications