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Usefulness of the genetic risk score to identify phenocopies in families with familial hypercholesterolemia?
Ghaleb, Youmna; Elbitar, Sandy; El Khoury, Petra; Bruckert, Eric; Carreau, Valérie; Carrié, Alain; Moulin, Philippe; Di-Filippo, Mathilde; Charriere, Sybil; Iliozer, Harout; Farnier, Michel; Luc, Gérald; Rabès, Jean-Pierre; Boileau, Catherine; Abifadel, Marianne; Varret, Mathilde.
Afiliación
  • Ghaleb Y; LVTS, INSERM U1148, Paris, France.
  • Elbitar S; Paris Diderot University, Paris7, France.
  • El Khoury P; Laboratory of Biochemistry and Molecular Therapeutics (LBTM), Faculty of Pharmacy and Pôle technologie Santé (PTS), Saint-Joseph University, Beirut, Lebanon.
  • Bruckert E; LVTS, INSERM U1148, Paris, France.
  • Carreau V; Paris Diderot University, Paris7, France.
  • Carrié A; Laboratory of Biochemistry and Molecular Therapeutics (LBTM), Faculty of Pharmacy and Pôle technologie Santé (PTS), Saint-Joseph University, Beirut, Lebanon.
  • Moulin P; LVTS, INSERM U1148, Paris, France.
  • Di-Filippo M; Laboratory of Biochemistry and Molecular Therapeutics (LBTM), Faculty of Pharmacy and Pôle technologie Santé (PTS), Saint-Joseph University, Beirut, Lebanon.
  • Charriere S; Department of Endocrinology and Cardiovascular Disease Prevention, AP-HP, La Pitié-Salpêtrière Hospital, ICAN, Paris, France.
  • Iliozer H; Department of Endocrinology and Cardiovascular Disease Prevention, AP-HP, La Pitié-Salpêtrière Hospital, ICAN, Paris, France.
  • Farnier M; Department of Biochemistry, AP-HP, La Pitié-Salpêtrière Hospital, Paris, France.
  • Luc G; Department of Endocrinology, Nutrition and Metabolic Diseases, Hospices Civils de Lyon, Louis Pradel Cardiovascular Hospital, Bron, France.
  • Rabès JP; Department of Biochemistry and Molecular Biology, Hospices Civils de Lyon, Bron, France.
  • Boileau C; Department of Endocrinology, Nutrition and Metabolic Diseases, Hospices Civils de Lyon, Louis Pradel Cardiovascular Hospital, Bron, France.
  • Abifadel M; Department of Endocrinology, Nutrition and Metabolic Diseases, Hospices Civils de Lyon, Louis Pradel Cardiovascular Hospital, Bron, France.
  • Varret M; Department of Cardiology and Point Médical, CHU Dijon Bourgogne, Dijon, France.
Eur J Hum Genet ; 26(4): 570-578, 2018 04.
Article en En | MEDLINE | ID: mdl-29374275
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fenotipo / Pruebas Genéticas / Predisposición Genética a la Enfermedad / Hipercolesterolemia Tipo de estudio: Etiology_studies / Evaluation_studies / Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Eur J Hum Genet Asunto de la revista: GENETICA MEDICA Año: 2018 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
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XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fenotipo / Pruebas Genéticas / Predisposición Genética a la Enfermedad / Hipercolesterolemia Tipo de estudio: Etiology_studies / Evaluation_studies / Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Eur J Hum Genet Asunto de la revista: GENETICA MEDICA Año: 2018 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Reino Unido