The ANO3/MUC15 locus is associated with eczema in families ascertained through asthma.
BACKGROUND
A previous genome-wide linkage scan in 295 families of the French Epidemiological Study on the Genetics and Environment of Asthma (EGEA) reported strong evidence of linkage of 11p14 to eczema.


OBJECTIVE
Our purpose was to conduct fine-scale mapping of the 11p14 region to identify the genetic variants associated with eczema.


METHODS
Association analyses were first conducted in the family sample from the French EGEA by using 2 methods: the family-based association method and logistic regression. Replication of the EGEA findings was sought in French Canadian and United Kingdom family samples, which, similarly to EGEA samples, were ascertained through asthma. We also tested for association in 2 German samples ascertained through eczema.


RESULTS
We found significant association of eczema with 11p14 genetic variants in the vicinity of the linkage peak in EGEA (P = 10(-4) for rs1050153 by using the family-based association method, which reached the multiple testing-corrected threshold of 10(-4); P = .003 with logistic regression). Pooled analysis of the 3 asthma-ascertained samples showed strong improvement in the evidence for association (P = 6 × 10(-6) for rs293974, P = 3 × 10(-5) for rs1050153, and P = 8 × 10(-5) for rs15783). No association was observed in the eczema-ascertained samples.


CONCLUSIONS
The significant single nucleotide polymorphisms are located within the overlapping anoctamin 3 (ANO3) and mucin 15 (MUC15) genes. Several lines of evidence suggest that MUC15 is a strong candidate for eczema. Further investigation is needed to confirm our findings and to better understand the role of the ANO3/MUC15 locus in eczema and its relationship with respect to asthma.
Genetic Variation and Human Diseases Unit, INSERM, U946, Paris, France; Université Paris, France. Marie-Helene.Dizier@inserm.fr
Marie-Hélène
MH
Dizier
Patricia
P
Margaritte-Jeannin
Anne-Marie
AM
Madore
Jorge
J
Esparza-Gordillo
Miriam
M
Moffatt
Eve
E
Corda
Florent
F
Monier
Michel
M
Guilloud-Bataille
Andre
A
Franke
Stephan
S
Weidinger
Isabella
I
Annesi-Maesano
Jocelyne
J
Just
Isabelle
I
Pin
Francine
F
Kauffmann
William
W
Cookson
Young-Ae
YA
Lee
Catherine
C
Laprise
Mark
M
Lathrop
Emmanuelle
E
Bouzigon
Florence
F
Demenais
D000293:Adolescent; D000328:Adult; D000483:Alleles; D000075368:Anoctamins; D001249:Asthma / Q000235:genetics*; D002648:Child; D018118:Chloride Channels / Q000235:genetics*; D004485:Eczema / Q000235:genetics*; D005190:Family; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D009077:Mucins / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics; D055815:Young Adult
C577591:ANO3 protein, human; D000075368:Anoctamins; D018118:Chloride Channels; C460499:MUC15 protein, human; D009077:Mucins