[HTML][HTML] Genome-wide association studies complemented with mechanistic biological studies identify sortilin 1 as a novel regulator of cholesterol trafficking
AJ Marian - Current atherosclerosis reports, 2011 - Springer
Current atherosclerosis reports, 2011•Springer
Methods: The methods include population genetic studies to test association of the
rs12740374 single nucleotide polymorphism (SNP) with plasma LDL-C levels; functional
studies to detect the effects of the locus SNP on expression levels of the genes located at the
1p13 locus; assessment of the effects of the nucleotide change on a C/EBPα binding site
and promoter activity; and in vivo genetic manipulation in mice to test effects of over-
expression or suppression of expression of SORT1 on plasma LDL-C levels. Results: The …
rs12740374 single nucleotide polymorphism (SNP) with plasma LDL-C levels; functional
studies to detect the effects of the locus SNP on expression levels of the genes located at the
1p13 locus; assessment of the effects of the nucleotide change on a C/EBPα binding site
and promoter activity; and in vivo genetic manipulation in mice to test effects of over-
expression or suppression of expression of SORT1 on plasma LDL-C levels. Results: The …
Methods: The methods include population genetic studies to test association of the rs12740374 single nucleotide polymorphism (SNP) with plasma LDL-C levels; functional studies to detect the effects of the locus SNP on expression levels of the genes located at the 1p13 locus; assessment of the effects of the nucleotide change on a C/EBPα binding site and promoter activity; and in vivo genetic manipulation in mice to test effects of over-expression or suppression of expression of SORT1 on plasma LDL-C levels.
Results: The minor allele of the rs12740374 SNP was associated with lower plasma LDL-C levels. The allele created a C/EBP (CCAAT/enhancer binding protein) transcription factor binding site, which was associated with enhanced hepatic expression of the SORT1 gene. Over-expression and suppression of expression of Sort 1 in mouse liver led to lower and higher plasma LDL-C and very low-density lipoprotein (VLDL) levels, respectively.
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