Association of CARD15 polymorphisms with atopy-related traits in a population-based cohort of Caucasian adults.
BACKGROUND
Influences of microbial pathogens are crucial for the maturation of the immune system. Caspase-recruitment domain containing protein 15 (CARD15) is a cytosolic receptor involved in bacterial recognition by antigen-presenting cells. CARD15 polymorphisms have been associated with Crohn's disease. Recently, associations with atopic phenotypes have been reported in children.


OBJECTIVE
Within a large population of German adults (n=1875), we evaluated eight CARD15 polymorphisms for associations with atopic phenotypes.


METHODS
Subjects were phenotyped by standardized questionnaires and interviews as well as total and allergen-specific IgE measurements. Genotyping was performed using matrix-assisted laser desorption ionization--time of flight mass spectrometry. Haplotypes were estimated using the SAS/Genetics module.


RESULTS
Subjects with a T allele at rs1077861 had a decreased risk of developing asthma (odds ratio OR=0.648, P=0.013), whereas the presence of an A allele at rs3135500 was significantly associated with an increased risk (OR=1.374, P=0.023). In addition, a CARD15 haplotype revealed to be protective against the development of asthma (OR=0.326, P=0.003). Subjects with an A allele at position rs5743266 or a T allele at rs2066842 had a significantly decreased risk of developing allergic rhinoconjunctivitis with ORs of 0.820 (P=0.049) and 0.801 (P=0.025). Polymorphism rs2066845 showed a significant association with increased total serum IgE (OR=2.155, P=0.006).


CONCLUSIONS
Genetic variants of CARD15 that might result in inappropriate immunomodulation are not only associated with autoimmune diseases but also with atopic disorders.
Weidinger
S
S
Department of Dermatology and Allergy Biederstein, Technical University Munich, Germany.
Klopp
N
N
Rümmler
L
L
Wagenpfeil
S
S
Baurecht
H J
HJ
Gauger
A
A
Darsow
U
U
Jakob
T
T
Novak
N
N
Schäfer
T
T
Heinrich
J
J
Behrendt
H
H
Wichmann
H E
HE
Ring
J
J
Illig
T
T
D000483:Alleles; D001249:Asthma / Q000235:genetics; D015331:Cohort Studies; D003233:Conjunctivitis, Allergic / Q000235:genetics; D003430:Cross-Sectional Studies; D003876:Dermatitis, Atopic / Q000235:genetics; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics*; D007073:Immunoglobulin E / Q000097:blood; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D053473:Nod2 Signaling Adaptor Protein; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics*; D012220:Rhinitis / Q000235:genetics; D012307:Risk Factors
D047908:Intracellular Signaling Peptides and Proteins; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D007073:Immunoglobulin E