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Predicted pathogenic mutations in STAP1 are not associated with clinically defined familial hypercholesterolemia.

Authors
  • Lamiquiz-Moneo, Itziar1
  • Restrepo-Córdoba, María Alejandra2
  • Mateo-Gallego, Rocío3
  • Bea, Ana María4
  • Del Pino Alberiche-Ruano, María5
  • García-Pavía, Pablo6
  • Cenarro, Ana4
  • Martín, Cesar7
  • Civeira, Fernando3
  • Sánchez-Hernández, Rosa María5
  • 1 Lipid Unit, Hospital Universitario Miguel Servet, Instituto de Investigación Sanitaria Aragón (IIS Aragón), CIBER Cardiovascular (CIBERCV), Zaragoza, Spain. Electronic address: [email protected] , (Spain)
  • 2 Heart Failure and Inherited Cardiac Diseases Unit, Department of Cardiology, Hospital Universitario Puerta de Hierro, CIBER Cardiovascular (CIBERCV), Madrid, Spain. , (Spain)
  • 3 Lipid Unit, Hospital Universitario Miguel Servet, Instituto de Investigación Sanitaria Aragón (IIS Aragón), CIBER Cardiovascular (CIBERCV), Zaragoza, Spain; Universidad de Zaragoza, Zaragoza, Spain. , (Spain)
  • 4 Lipid Unit, Hospital Universitario Miguel Servet, Instituto de Investigación Sanitaria Aragón (IIS Aragón), CIBER Cardiovascular (CIBERCV), Zaragoza, Spain. , (Spain)
  • 5 Endocrinology Department, Hospital Universitario Insular de Gran Canaria, Instituto Universitario de Investigación Biomédica y de la Salud de la Universidad de Las Palmas de Gran Canaria, Las Palmas, Spain. , (Spain)
  • 6 Heart Failure and Inherited Cardiac Diseases Unit, Department of Cardiology, Hospital Universitario Puerta de Hierro, CIBER Cardiovascular (CIBERCV), Madrid, Spain; Universidad Francisco de Vitoria (UFV), Pozuelo de Alarcon, Spain. , (Spain)
  • 7 Instituto Biofisika (UPV/EHU, CSIC) and Departamento de Bioquímica, Universidad del País Vasco, Bilbao, Spain. , (Spain)
Type
Published Article
Journal
Atherosclerosis
Publication Date
Nov 29, 2019
Volume
292
Pages
143–151
Identifiers
DOI: 10.1016/j.atherosclerosis.2019.11.025
PMID: 31809983
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Autosomal dominant familial hypercholesterolemia (FH) is caused by mutations in LDLR,APOB and PCSK9. Two new putative loci causing FH have been identified recently, the p.(Leu167del) mutation in APOE and new mutations in the signal transducing adaptor family member STAP1. We aimed at investigating the role of STAP1 mutations in the etiology of FH. We sequenced LDLR, APOB, PCSK9, LDLRAP1, APOE, LIPA and STAP1 with the LipidInCode platform in 400 unrelated subjects from Spain with a clinical diagnosis of FH. All subjects carrying rare predicted pathogenic variants in STAP1 gene, described as pathogenic by at least three bioinformatic analysis and having an allelic frequency lower than 1% in general population, were selected for family study. Available relatives were recruited, including both hypercholesterolemic and non-hypercholesterolemic family members. Sequencing analysis of STAP1 gene revealed seventeen rare variants, four of them being described as pathogenic by bioinformatic analysis. We studied the cosegregation with hypercholesterolemia of four rare predicted pathogenic variants, c.-60A > G, p.(Arg12His), p.(Glu97Asp), p.(Pro176Ser) in seven families. We did not observe any cosegregation between genotype and phenotype, even carriers of rare variants in STAP1 had lower LDL cholesterol levels than non-carriers. This study analyzes the family cosegregation of four rare predicted pathogenic variants of STAP1, p.(Arg12His), p.(Glu97Asp), p.(Pro176Ser) and c.-60A > G, in seven families, showing absence of cosegregation in all of them. These results would suggest that STAP1 gene is not involved in hypercholesterolemia of these families. Copyright © 2019 Elsevier B.V. All rights reserved.

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