Integrin β3 genotype influences asthma and allergy phenotypes in the first 6 years of life

被引:26
作者
Thompson, Emma E.
Pan, Lin
Ostrovnaya, Irina
Weiss, Lauren A.
Gern, James E.
Lemanske, Robert F., Jr.
Nicolae, Dan L.
Ober, Carole
机构
[1] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA
[2] Univ Chicago, Dept Stat, Chicago, IL 60637 USA
[3] Univ Chicago, Dept Med, Chicago, IL 60637 USA
[4] Univ Wisconsin, Dept Med, Madison, WI USA
[5] Univ Wisconsin, Dept Pediat, Madison, WI USA
关键词
asthma; allergy; noncoding variation; integrin; viral respiratory illness;
D O I
10.1016/j.jaci.2007.03.029
中图分类号
R392 [医学免疫学];
学科分类号
100102 ;
摘要
Background: The integrin beta 3 gene (ITGB3) encodes a subunit of the platelet and monocyte-specific fibrinogen receptor and the widely expressed vitronectin receptor, which have diverse roles in cell migration, adhesion, and signaling. Previous work from our laboratory reported associations between single nucleotide polymorphisms (SNPs) in ITGB3 and asthma and allergic sensitization in 4 populations. Objective: To examine whether SNPs in ITGB3 are associated with the development of asthma and allergic phenotypes in early life. Methods: We typed 13 SNPs in 206 children participating in a birth cohort study and tested for associations with asthma and allergy phenotypes in the first 6 years of life. Results: Our study revealed significant associations between SNPs in ITGB3 and asthma, wheezing, and IgE levels, suggesting an early role for this gene in the development of asthma and allergy. In particular, SNPs at the 3' end of the gene were significantly associated with IgE levels beginning at 1 year of age, whereas a SNP in intron I showed significant interaction effects with viral respiratory illness in infancy on asthma susceptibility. Conclusion: Our results suggest that genetic variation in ITGB3 contributes to asthma susceptibility and allergic sensitization, and that the effects of this gene begin early in life. Similar to our earlier study, different SNPs in the gene are associated with asthma and IgE. Clinical implications: ITGB3 may play an important role in the development of asthma and allergy and may represent a potential therapeutic target for the treatment of these disorders.
引用
收藏
页码:1423 / 1429
页数:7
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