Title :

Usefulness of the genetic risk score to identify phenocopies in families with familial hypercholesterolemia?

Author(s) :

Ghaleb, Youmna [Auteur]
Elbitar, Sandy [Auteur]
El Khoury, Petra [Auteur]
Bruckert, Eric [Auteur]
Carreau, Valérie [Auteur]
Carrie, Alain [Auteur]
Moulin, Philippe [Auteur]
Di-Filippo, Mathilde [Auteur]
Charriere, Sybil [Auteur]
Iliozer, Harout [Auteur]
Farnier, Michel [Auteur]
Luc, Gerald [Auteur]
Rabes, Jean-Pierre [Auteur]
Boileau, Catherine [Auteur]
Abifadel, Marianne [Auteur]
Varret, Mathilde [Auteur]

Journal title :

European journal of human genetics . EJHG

Abbreviated title :

Eur. J. Hum. Genet.

Publication date :

2018-01-26

ISSN :

1476-5438

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

Familial hypercholesterolemia (FH) is caused by mutations in LDLR (low-density lipoprotein receptor), APOB (apolipoprotein B), PCSK9 (proprotein convertase subtilisin/kexin type 9), or APOE (apolipoprotein E) genes in ...
Show more >Familial hypercholesterolemia (FH) is caused by mutations in LDLR (low-density lipoprotein receptor), APOB (apolipoprotein B), PCSK9 (proprotein convertase subtilisin/kexin type 9), or APOE (apolipoprotein E) genes in approximately 80% of the cases. Polygenic forms of hypercholesterolemia may be present among patients clinically diagnosed with FH but with no identified mutation (FH mutation-negative (FH/M-)). To address whether polygenic forms may explain phenocopies in FH families, we calculated a 6-single-nucleotide polymorphism (SNP) genetic risk score (GRS) in all members from five French FH families where a mutation was identified (FH/M+) as well as some phenocopies (FH/M-). In two families, three FH/M- patients present a high GRS suggesting a polygenic hypercholesterolemia for these phenocopies. However, a high GRS is also observed in nine FH/M+ patients and in four unaffected relatives from three families. These observations indicate that the GRS does not seem to be a good diagnostic tool at the individual level. Nevertheless, the GRS seems to be a contributor of the severity of hypercholesterolemia since patients who cumulate a mutation and a high GRS exhibit higher low-density lipoprotein cholesterol levels when compared to patients with only FH (p = 0.054) or only polygenic hypercholesterolemia (p = 0.0039). In conclusion, the GRS can be used as a marker of the severity of hypercholesterolemia but does not seem to be a reliable tool to distinguish phenocopies within FH families.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

CHU Lille
Université de Lille

Collections :

• METRICS : Evaluation des technologies de santé et des pratiques médicales - ULR 2694

Submission date :

2019-12-09T16:50:44Z