title: A presumptive new locus for autosomal dominant hypercholesterolemia mapping to 8q24.22.
abstract: 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.
authors.affiliation: Unidad de Lípidos and Laboratorio de Investigación Molecular, Hospital Universitario Miguel Servet, Instituto Aragonés de Ciencias de Salud (I+CS), Zaragoza, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Cenarro
authors.forename: A-L
authors.initials: AL
authors.lastname: García-Otín
authors.forename: M T
authors.initials: MT
authors.lastname: Tejedor
authors.forename: M
authors.initials: M
authors.lastname: Solanas
authors.forename: E
authors.initials: E
authors.lastname: Jarauta
authors.forename: C
authors.initials: C
authors.lastname: Junquera
authors.forename: E
authors.initials: E
authors.lastname: Ros
authors.forename: P
authors.initials: P
authors.lastname: Mozas
authors.forename: J
authors.initials: J
authors.lastname: Puzo
authors.forename: M
authors.initials: M
authors.lastname: Pocoví
authors.forename: F
authors.initials: F
authors.lastname: Civeira
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002874:Chromosome Mapping; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D005260:Female; D056426:Genetic Loci; D006239:Haplotypes; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000235:genetics*; D008297:Male; D009154:Mutation; D010375:Pedigree