Association of NOD1 polymorphisms with atopic eczema and related phenotypes

Background: Interactions with microbial pathogens are crucial for the maturation of the immune system. The nucleotide-binding oligomerization domain protein 1 (NOD1) is a cytosolic receptor sensing a muropeptide found mostly in gram-negative bacterial peptidoglycans. NOD1 is located on chromosome 7p14-p15, a region that has been linked with atopy. Recently, polymorphisms of the closely related NOD2 have been associated with atopy-related traits. Objectives: Within a large population-based cohort of German adults (n = 1417), a case-control population for atopic eczema (n = 454), and a large cohort of parent-offspring trios for atopic eczema (189 trios), we evaluated 11 NOD1 polymorphisms for associations with atopic phenotypes. Methods: Subjects were phenotyped by standardized questionnaires and interviews, skin examination, and serum IgE measurements. Genotyping was performed by using matrix-assisted laser desorption ionization-time of flight mass spectrometry. Results: Analyses revealed significant association of one NOD1 haplotype with atopic eczema in the population-based cohort (P = .004) and the case-control population (P = .003). Another NOD1 haplotype was associated with decreased total IgE (P = .008). In addition, significant associations with total serum IgE levels were observed for polymorphisms rs2907748 (P = .006), rs2907749 (P = .012), and rs2075822 (P = .018). These polymorphisms were significantly associated with atopic eczema and asthma in the family-based association analyses (P = .001-043). Seven polymorphisms showed significant transmission distortion for total IgE levels (P values < .0001-.029). Conclusion: These data indicate that genetic variants within NOD1 are important determinants of atopy susceptibility.