Journal Article

Genetic Control of Serum IgE Levels and Asthma: Linkage and Linkage Disequilibrium Studies in an Isolated Population

Tarja Laitinen, Paula Kauppi, Jaakko Ignatius, Tarja Ruotsalainen, Mark J. Daly, Helena Kääriäinen, Leonid Kruglyak, Hannu Laitinen, Albert de la Chapelle, Eric S. Lander, Lauri A. Laitinen and Juha Kere

in Human Molecular Genetics

Volume 6, issue 12, pages 2069-2076
Published in print November 1997 | ISSN: 0964-6906
Published online November 1997 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/6.12.2069
Genetic Control of Serum IgE Levels and Asthma: Linkage and Linkage Disequilibrium Studies in an Isolated Population

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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.

Journal Article.  4899 words.  Illustrated.

Subjects: Genetics and Genomics

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