In 2001, fine mapping confirmed that nucleotide-binding oligomerization domain containing 2 (NOD2)/caspase recruitment domain family member 15 (CARD15) of the IBD1 locus was related to CD and three single-nucleotide polymorphisms (SNPs) of NOD2/CARD15, rs2066844 (p.Arg702Trp), rs2066845 (p.Gly908Arg), and rs2066847 (p.Leu1007fsinsC), were significantly associated with CD [21]. This evidence concerns the gene NOD2 and Cowden disease.