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Haplotypes of the interleukin-4 receptor alpha chain gene associate with susceptibility to and severity of atopic asthma

Artikel i vetenskaplig tidskrift
Författare Ann-Marie Hytönen
Olle Löwhagen
Monica Arvidsson
Barbro Balder
A. L. Björk
S. Lindgren
Mirjana Hahn-Zoric
Lars Åke Hanson
L. Padyukov
Publicerad i Clin Exp Allergy
Volym 34
Nummer/häfte 10
Sidor 1570-5.
Publiceringsår 2004
Publicerad vid Institutionen för laboratoriemedicin, Avdelningen för klinisk immunologi
Institutionen för invärtesmedicin, Avdelningen för lungmedicin och allergologi
Sidor 1570-5.
Språk en
Länkar www.ncbi.nlm.nih.gov/entrez/query.f...
Ämneskategorier Lungmedicin och allergi

Sammanfattning

Summary Background Development of asthma is likely to depend on a complex interaction between environmental and genetic factors. Several groups have suggested the gene of the IL-4 receptor alpha chain (IL4R) as a candidate gene for the development of asthma, although association with single polymorphisms has shown contradicting results. Objective We chose to analyse IL4R gene haplotypes and assess their possible relevance in susceptibility to asthma and to certain clinical phenotypes. Methods IL4R gene haplotypes were analysed, based on the three markers C-3223T, Q551R and I50V, using the expectation-maximization algorithm, in 170 atopic asthma patients and 350 controls, all adult Swedish Caucasians. Results Our data showed significantly higher levels of soluble IL-4R (sIL-4R) in asthma patients compared with controls (P<0.0001). Furthermore, we showed a significant association between the IL4R haplotype containing the alleles T-3223, V50 and R551 (TVR) of the IL4R gene, and susceptibility to atopic asthma, with a frequency of 6.5% in the patients compared with 1% in the controls (P<0.0005). A subgroup of patients with heterozygous or homozygous state for the T-3223, V50 and R551 alleles, also had lower levels of sIL-4R in their circulation compared with patients with homozygous state in the C-3223, I50 and Q551 alleles (P<0.05) and showed less severe asthma according to lung function test (P<0.05). Analysis of single markers showed the T-3223 IL4R allele to associate with lower serum levels of sIL-4 receptor (P<0.0001) and patients carrying the T allele also had more symptoms of active asthma (wheezing, P<0.01; coughing, P<0.05 and breathing difficulties, P<0.01). Conclusion Our data suggest that asthmatic patients with low levels of sIL-4 receptor may represent a genetically distinct subgroup of atopic asthma. TVR haplotype analyses confirm the importance of IL4R as a candidate gene for susceptibility to asthma. This finding may have implications for the understanding of the pathogenesis of asthma and possibly for the development of more specific therapies.

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