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

作者：Cenarro A; Garcia Otin A L; Tejedor M T; Solanas M; Jarauta E; Junquera C; Ros E; Mozas P; Puzo J; Pocovi M; Civeira F^*

来源：Clinical Genetics, 2011, 79(5): 475-481.

DOI：10.1111/j.1399-0004.2010.01485.x

• autosomal dominant hypercholesterolemia
• genome-wide analysis
• haplotype analyses
• LDL-cholesterol

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.

• 出版日期2011-5