A presumptive new locus for autosomal dominant hypercholesterolemia mapping to 8q24.22

Authors

  • A Cenarro,

    1. Unidad de Lípidos and Laboratorio de Investigación Molecular, Hospital Universitario Miguel Servet, Instituto Aragonés de Ciencias de la Salud (I+CS), Zaragoza, Spain
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    • These authors contributed equally to this work.

  • A-L García-Otín,

    1. Unidad de Lípidos and Laboratorio de Investigación Molecular, Hospital Universitario Miguel Servet, Instituto Aragonés de Ciencias de la Salud (I+CS), Zaragoza, Spain
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    • These authors contributed equally to this work.

  • MT Tejedor,

    1. Departamento de Anatomía, Embriología y Genética, Universidad de Zaragoza, Zaragoza, Spain
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  • M Solanas,

    1. Unidad de Lípidos and Laboratorio de Investigación Molecular, Hospital Universitario Miguel Servet, Instituto Aragonés de Ciencias de la Salud (I+CS), Zaragoza, Spain
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  • E Jarauta,

    1. Unidad de Lípidos and Laboratorio de Investigación Molecular, Hospital Universitario Miguel Servet, Instituto Aragonés de Ciencias de la Salud (I+CS), Zaragoza, Spain
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  • C Junquera,

    1. Progenika Biopharma S.A., Vizcaya, Spain
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  • E Ros,

    1. Unitat de Lípids, Servei d’Endocrinologia i Nutrició, Institut d’Investigacions Biomèdiques August Pi i Sunyer, Hospital Clínic, Barcelona, Spain
    2. Ciber CB06/03 Fisiopatología Obesidad y Nutrición, Instituto de Salud Carlos III, Barcelona, Spain
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  • P Mozas,

    1. Departamento de Bioquímica, Biología Molecular y Celular, CIBERER, Universidad de Zaragoza, Zaragoza, Spain
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  • J Puzo,

    1. Unidad de Lípidos y Laboratorio de Bioquímica, Hospital San Jorge, Huesca, Spain
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  • M Pocoví,

    1. Departamento de Bioquímica, Biología Molecular y Celular, CIBERER, Universidad de Zaragoza, Zaragoza, Spain
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  • F Civeira

    Corresponding author
    1. Unidad de Lípidos and Laboratorio de Investigación Molecular, Hospital Universitario Miguel Servet, Instituto Aragonés de Ciencias de la Salud (I+CS), Zaragoza, Spain
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Fernando Civeira, MD, PhD, Unidad de Lípidos and Laboratorio de Investigación Molecular, Hospital Universitario Miguel Servet, Instituto Aragonés de Ciencias de la Salud (I+CS), P° Isabel la Católica, 1-3, 50009 Zaragoza, Spain.
Tel.: +34976765500;
fax: +34976369985;
e-mail: civeira@unizar.es

Abstract

Cenarro A, García-Otín A-L, Tejedor MT, Solanas M, Jarauta E, Junquera C, Ros E, Mozas P, Puzo J, Pocoví M, Civeira F. A presumptive new locus for autosomal dominant hypercholesterolemia mapping to 8q24.22.

Molecular testing of patients with autosomal dominant hypercholesterolemia (ADH) fails to detect a causal functional mutation in 15.25% of subjects. We studied an ADH pedigree in which known ADH-causing genes (LDLR, APOB and PCSK9) were excluded. Genome-wide analysis on 15 family members detected significant association for ADH and dbSNP RS ID rs965814 (G/A), located in 8q24.22 cytoband. ADH was significantly associated to rs965814 G allele (p < 0.05) in a case–control study based on 200 unrelated ADH subjects without LDLR or APOB gene defects and 198 normolipidemic controls. We chose 24 markers for a detailed analysis of 8q24.22 cytoband, now based on an extended set of family members (21 individuals). One particular 24 marker haplotype was significantly associated to both higher total and low-density lipoprotein-cholesterol concentrations. Similar results were found for a shorter haplotype, composed of the distal six markers from the complete haplotype. Therefore, a presumptive new locus for ADH could be located in 8q24.22 cytoband, a region not previously linked or associated to ADH.

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