These authors contributed equally to this work.
A presumptive new locus for autosomal dominant hypercholesterolemia mapping to 8q24.22
Article first published online: 15 JUN 2010
© 2010 John Wiley & Sons A/S
Volume 79, Issue 5, pages 475–481, May 2011
How to Cite
Cenarro, A., García-Otín, A.-L., Tejedor, M., Solanas, M., Jarauta, E., Junquera, C., Ros, E., Mozas, P., Puzo, J., Pocoví, M. and Civeira, F. (2011), A presumptive new locus for autosomal dominant hypercholesterolemia mapping to 8q24.22. Clinical Genetics, 79: 475–481. doi: 10.1111/j.1399-0004.2010.01485.x
- Issue published online: 7 APR 2011
- Article first published online: 15 JUN 2010
- Received 8 February 2010, revised and accepted for publication 9 June 2010
- autosomal dominant hypercholesterolemia;
- genome-wide analysis;
- haplotype analyses;
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.