Increased susceptibility to ACS has been associated with the T-786C SNP in the NOS3 gene in females.82 Gender specific disease modifications in the endothelial NOS3 have been proposed as explanation for these modifications.83 It is suggested that the differences between sexes could possibly be explained by modulation of NOS3 activity through circulating estrogen, resulting in differences of NO formation in pulmonary vascular endothelium between females and males. This evidence concerns the gene NOS3 and acute chest syndrome.