NOD2 and Cowden disease: However, approximately 11%–14% of white Europeans are heterozygous and 0.4%–0.9% homozygous or compound-heterozygous for CD-risk-variant NOD2 but remain healthy, which reinforces the role for coexistent genetic or environmental factors in initiation of CD.15,16 The association of defective antibacterial mechanisms with CD-associated polymorphisms in NOD2 suggest that the presence of these variants may influence the nature of the microbiota over time.