Premium
A presumptive new locus for autosomal dominant hypercholesterolemia mapping to 8q24.22
Author(s) -
Cenarro A,
GarcíaOtín AL,
Tejedor MT,
Solanas M,
Jarauta E,
Junquera C,
Ros E,
Mozas P,
Puzo J,
Pocoví M,
Civeira F
Publication year - 2011
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/j.1399-0004.2010.01485.x
Subject(s) - haplotype , locus (genetics) , genetics , biology , allele , apolipoprotein b , genetic linkage , gene , cholesterol , endocrinology
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.