Based on the hypothetic mechanism that these high-risk genotypes were associated with an increasing risk of stroke disease by mimicking ischemic contracture on reduced vascular hyperpermeability to inhibit NO generation, the modified effects of hypercholesterolemia, alcohol drinking, and heavy cigarette smoking on LAA stroke risk would be more significant in carriers of high-risk genotypes of eNOS and Cav-1. The gene discussed is NOS3; the disease is Stroke.