Firstly, Singh et al. demonstrated that different genetic variants of the 3 isoforms that synthesize nitric oxide (NOS) (endothelial NOS-eNOS, inducible NOS-iNOS and neuronal NOS-nNOS), the most important known inhibitory neurotransmitter of the esophageal myenteric plexus, could represent risk factors for the achalasia development. Here, NOS3 is linked to Achalasia.