No linkage and association of atopy to chromosome 16 including the interleukin-4 receptor gene.
BACKGROUND
Several susceptibility genes for atopy have been suggested in recent years. Few have been investigated as intensively as the interleukin-4-receptor alpha (IL4Ralpha) gene on chromosome 16. The results remain in dispute. Therefore, in a robust design, we tested for association of type I allergy to the IL4R variations I50V and Q576R, and investigated chromosome 16 for atopy candidate regions in general.


METHODS
We identified 100 Danish allergy sib-pair families. Five conservative phenotypes for type I allergy were defined and evaluated. The IL4R variations were genotyped in trios and evaluated by the transmission disequilibrium test (TDT). Multipoint linkage analysis and exclusion mapping were conducted with sib-pairs analyzed for 17 microsatellite markers.


RESULTS
No evidence for association or linkage to the IL4R polymorphisms was found (P values: 0.12-0.90). Linkage analysis did not support linkage of any of the phenotypes to chromosome 16. Major parts of chromosome 16 were excluded as candidate regions harboring oligogenes for type I allergy.


CONCLUSIONS
We found chromosome 16 unlikely to harbor strong candidate genes for type I allergy. The role of the IL4Ralpha gene in the inheritance of atopy was insignificant in the Danish population. The use of conservative allergy phenotypes in the search for genes predisposing to atopic disease was discussed.
Haagerup
A
A
Institute of Human Genetics, Bartholin Building, Aarhus University, DK-8000 Aarhus C, Denmark.
Bjerke
T
T
Schiøtz
P O
PO
Dahl
R
R
Binderup
H G
HG
Kruse
T A
TA
D002648:Child; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D014644:Genetic Variation; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics*; D008126:Lod Score; D008297:Male; D019948:Receptors, Interleukin-4 / Q000235:genetics*
D019948:Receptors, Interleukin-4