Departments of Biochemistry and Medicine, Robarts Research Institute and Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada.
Bioessays. 2011 Jun;33(6):430-7. doi: 10.1002/bies.201100003. Epub 2011 Apr 4.
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.
血浆中低密度脂蛋白（LDL）胆固醇（C）的浓度是心血管疾病风险的关键决定因素，人类遗传研究长期以来一直致力于阐明调节 LDL 代谢的途径。大规模全基因组关联研究（GWAS）表明，常见遗传变异与人群中的 LDL-C 相关，SORT1 与 LDL 代谢有关。使用适合理解常见变异如何改变表型表达的机制的实验范式和标准，三篇最近的出版物提出了相互矛盾甚至相互矛盾的发现。有趣的是，尽管这些报告都将 SORT1 与 LDL 代谢联系起来，但它们并没有就解释这种关联的机制达成一致。在这里，我们回顾了 SORT1 的最近机制研究 - 这是第一个被 GWAS 确定为决定血浆 LDL-C 的基因，以进行机制评估。
