NOTCH3 and ischemic stroke: In contrast, benign polymorphisms reported in this meta-analysis, i.e., NOTCH3 rs1043994, rs3515188 and rs1044009, were unable to exert any gain-of function or loss-of function on the NOTCH3 protein [14] and this may explain why these NOTCH3 polymorphisms were not associated with ischemic stroke risk in this meta-analysis.