Human Molecular Genetics, Vol 6, 2069-2076, Copyright © 1997 by Oxford University Press
T Laitinen, P Kauppi, J Ignatius, T Ruotsalainen, MJ Daly, H Kaariainen, L Kruglyak, H Laitinen, A de la Chapelle, ES Lander, LA Laitinen and J Kere
Immunoglobulin E (IgE) concentration in serum is elevated in atopic
diseases such as asthma. A large genomic region on chromosome 5 has
previously been implicated in the control of IgE levels and bronchial
hyperreactivity and may, therefore, harbor genes predisposing to asthma. In
an effort to confirm this linkage and to delimit the critical region, we
took advantage of an isolated founder subpopulation in Finland to study
genetic linkage and haplotype associations. Sixteen polymorphic markers,
including the Interleukin-4 and -9 genes (IL4, IL9), were physically
ordered and genotyped in 157 nuclear families. Genetic linkage studies
involving sib- and cousin-pair analyses found no evidence of genetic
linkage between markers in 5q and either serum IgE levels or asthma.
Haplotype association studies were also performed. Although initial
inspection suggested the possibility of linkage disequilibrium in the
region of IL9, we developed a rigorous permutation test for assessing
association and determined that the association was no greater than would
be expected by chance. Sequence analysis of the IL9 gene in three patients
sharing a possibly conserved haplotype revealed a T113M coding
polymorphism, but this variant showed no association with either serum IgE
levels or asthma. We conclude that allelic variation at chromosome 5q31 is
not likely to contribute to inheritance of serum IgE levels or the
development of asthma in this Finnish subpopulation.
ARTICLES
Genetic control of serum IgE levels and asthma: linkage and linkage disequilibrium studies in an isolated population
Department of Medical Genetics, Haartman Institute, Haartmaninkatu 3, 00014 University of Helsinki, Helsinki, Finland.
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