HMGCR and familial hypercholesterolemia: Elevated homocysteine can activate transcription factors [nuclear factor Y (NF-Y), cyclic adenosine monophosphate response element-binding protein (CREB), sterol regulatory element-binding protein 2 (SREBP-2)], increasing mRNA expression and activity of HMG-CoA reductase, promoting hepatic lipid accumulation, and ultimately contributing to hypercholesterolemia (96).