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.


OBJECTIVE
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).


CONCLUSIONS
These data indicate that genetic variants within NOD1 are important determinants of atopy susceptibility.
Weidinger
Stephan
S
The Department of Dermatology and Allergy Biederstein, Technical University, Munich, Germany. weidinger@lrz.tum.de
Klopp
Norman
N
Rummler
Lars
L
Wagenpfeil
Stefan
S
Novak
Natalija
N
Baurecht
Hans-Joerg
HJ
Groer
Werner
W
Darsow
Ulf
U
Heinrich
Joachim
J
Gauger
Anke
A
Schafer
Torsten
T
Jakob
Thilo
T
Behrendt
Heidrun
H
Wichmann
Hans-Erich
HE
Ring
Johannes
J
Illig
Thomas
T
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D001249:Asthma / Q000235:genetics; D016022:Case-Control Studies; D017931:DNA Primers; D003876:Dermatitis, Atopic / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D053474:Nod1 Signaling Adaptor Protein; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D048868:Adaptor Proteins, Signal Transducing; D017931:DNA Primers; C119067:NOD1 protein, human; D053474:Nod1 Signaling Adaptor Protein; D007073:Immunoglobulin E