Linkage and allelic association of atopy and markers flanking the IL4-receptor gene.
BACKGROUND
Atopy, a clinical syndrome characterized by heightened IgE responsiveness, is largely determined by genetic factors. The disease may well be heterogeneous but the mode of inheritance is unknown. Several genes have been named which affected IgE responsiveness. However, results are conflicting reflecting heterogeneity and a complicated inheritance pattern of the atopic syndrome. In 1994 linkage of the 5q32 gene region and elevated total IgE levels were reported, leaving the IL4 gene as a prominent candidate.


OBJECTIVE
We were interested in a possible involvement of the IL4-receptor gene in the development of atopy.


METHODS
We employed sib-pair linkage analysis using highly polymorphic microsatellite markers within and flanking the IL4 receptor gene in atopic families, characterized for specific sensitization to inhalant allergens and elevated total serum IgE. Allele sizes were determined for all microsatellite probes to allow transmission disequilibrium analysis.


RESULTS
We found significant sharing of maternal but not paternal alleles in affected sibs from two independent populations, both of which presented enhanced IgE responsiveness. Linkage and maternal inheritance could be confirmed by transmission disequilibrium analysis.


CONCLUSIONS
We conclude from our findings that maternal inheritance of a gene in the chromosome 16p12 region increases the risk for enhanced IgE responsiveness. The most prominent candidate in this region is represented by the IL4 receptor gene.
Deichmann
K A
KA
University Children's Hospital, University of Freiburg, Germany.
Heinzmann
A
A
Forster
J
J
Dischinger
S
S
Mehl
C
C
Brueggenolte
E
E
Hildebrandt
F
F
Moseler
M
M
Kuehr
J
J
D000293:Adolescent; D000328:Adult; D000483:Alleles; D002648:Child; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics; D005192:Family Health; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000235:genetics*; D007073:Immunoglobulin E / Q000097:blood / Q000235:genetics; D008297:Male; D019948:Receptors, Interleukin-4 / Q000235:genetics*; D012737:Sex Factors
D005819:Genetic Markers; D019948:Receptors, Interleukin-4; D007073:Immunoglobulin E