Division of Endocrinology, Diabetes and Metabolism, University of Cincinnati, Cincinnati, OH, USA.
Department of Pathology, University of Cincinnati, Cincinnati, OH, USA.
BMC Med Genet. 2020 Nov 23;21(1):234. doi: 10.1186/s12881-020-01176-x.
Autosomal dominant familial hypercholesterolemia (ADH; MIM#143890) is one of the most common monogenic disorders characterized by elevated circulatory LDL cholesterol. Initial studies in humans with ADH identified a potential relationship with variants of the gene encoding signal transducing adaptor family member protein 1 (STAP1; MIM#604298). However, subsequent studies have been contradictory. In this study, mice lacking global Stap1 expression (Stap1) were characterized under standard chow and a 42% kcal western diet (WD).
Mice were studied for changes in different metabolic parameters before and after a 16-week WD regime. Growth curves, body fats, circulatory lipids, parameters of glucose homeostasis, and liver architecture were studied for comparisons.
Surprisingly, Stap1 mice fed the 16-week WD demonstrated no marked differences in any of the metabolic parameters compared to Stap1 mice. Furthermore, hepatic architecture and cholesterol content in FPLC-isolated lipoprotein fractions also remained comparable to wild-type mice.
These results strongly suggest that STAP1 does not alter lipid levels, that a western diet did not exacerbate a lipid disorder in Stap1 deficient mice and support the contention that it is not causative for hyperlipidemia in ADH patients. These results support other published studies also questioning the role of this locus in human hypercholesterolemia.
常染色体显性家族性高胆固醇血症（ADH；MIM#143890）是最常见的单基因疾病之一，其特征为循环 LDL 胆固醇升高。最初对 ADH 患者的研究发现，信号转导衔接子家族成员蛋白 1（STAP1；MIM#604298）基因编码变体与该疾病之间可能存在关联。然而，随后的研究结果却相互矛盾。在这项研究中，研究人员对缺乏全局 Stap1 表达（Stap1）的小鼠在标准饲料和 42%热量西方饮食（WD）下的特征进行了研究。
在进行为期 16 周的 WD 饮食方案之前和之后，对小鼠的不同代谢参数变化进行了研究。对生长曲线、体脂肪、循环脂质、葡萄糖稳态参数和肝脏结构进行了研究，以进行比较。
令人惊讶的是，与 Stap1 小鼠相比，喂食 16 周 WD 的 Stap1 小鼠在任何代谢参数上均无明显差异。此外，FPLC 分离的脂蛋白部分的肝结构和胆固醇含量也与野生型小鼠相当。
这些结果强烈表明 STAP1 不会改变脂质水平，WD 饮食不会使 Stap1 缺乏的小鼠脂质代谢紊乱恶化，并支持 STAP1 基因不是 ADH 患者发生高脂血症的原因的观点。这些结果支持了其他质疑该基因座在人类高胆固醇血症中作用的已发表研究。
