Even though an NLRP3 genetic susceptibility was found in this population, careful analysis of the results show that, differently from the study by Villani and coworkers, the NLRP3 SNP associated with CD was a gain-of-function polymorphism, possibly promoting the production of mature IL-1β with subsequent induction of caspase-1 activity. This evidence concerns the gene NLRP3 and Cowden disease.