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Sortilin: An unusual suspect in cholesterol metabolism
Author(s) -
Dubé Joseph B.,
Johansen Christopher T.,
Hegele Robert A.
Publication year - 2011
Publication title -
bioessays
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.175
H-Index - 184
eISSN - 1521-1878
pISSN - 0265-9247
DOI - 10.1002/bies.201100003
Subject(s) - genome wide association study , biology , genetic association , mechanism (biology) , genetics , phenotype , genetic variation , gene , computational biology , single nucleotide polymorphism , genotype , philosophy , epistemology
The concentration of low‐density lipoprotein (LDL) cholesterol (C) in plasma is a key determinant of cardiovascular disease risk and human genetic studies have long endeavoured to elucidate the pathways that regulate LDL metabolism. Massive genome‐wide association studies (GWASs) of common genetic variation associated with LDL‐C in the population have implicated SORT1 in LDL metabolism. Using experimental paradigms and standards appropriate for understanding the mechanisms by which common variants alter phenotypic expression, three recent publications have presented divergent and even contradictory findings. Interestingly, although these reports each linked SORT1 to LDL metabolism, they did not agree on a mechanism to explain the association. Here, we review recent mechanistic studies of SORT1 – the first gene identified by GWAS as a determinant of plasma LDL‐C to be evaluated mechanistically.