Thompson Emma E, Pan Lin, Ostrovnaya Irina, Weiss Lauren A, Gern James E, Lemanske Robert F, Nicolae Dan L, Ober Carole
Department of Human Genetics, University of Chicago, Chicago, Ill., USA.
J Allergy Clin Immunol. 2007 Jun;119(6):1423-9. doi: 10.1016/j.jaci.2007.03.029.
The integrin beta3 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.
To examine whether SNPs in ITGB3 are associated with the development of asthma and allergic phenotypes in early life.
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.
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 1 showed significant interaction effects with viral respiratory illness in infancy on asthma susceptibility.
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.
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.
整合素β3基因(ITGB3)编码血小板和单核细胞特异性纤维蛋白原受体以及广泛表达的玻连蛋白受体的一个亚基,这些受体在细胞迁移、黏附和信号传导中具有多种作用。我们实验室之前的研究报道了ITGB3单核苷酸多态性(SNP)与4个群体中的哮喘和过敏致敏之间的关联。
研究ITGB3中的SNP是否与早期生活中哮喘和过敏表型的发生有关。
我们对参与一项出生队列研究的206名儿童的13个SNP进行了基因分型,并测试了其与生命最初6年中哮喘和过敏表型的关联。
我们的研究揭示了ITGB3中的SNP与哮喘、喘息和IgE水平之间存在显著关联,表明该基因在哮喘和过敏的发生中起早期作用。特别是,基因3'端的SNP与1岁开始的IgE水平显著相关,而内含子1中的一个SNP在婴儿期病毒呼吸道疾病对哮喘易感性方面显示出显著的交互作用。
我们的结果表明,ITGB3的基因变异导致哮喘易感性和过敏致敏,且该基因的作用在生命早期就已开始。与我们早期的研究相似,该基因中的不同SNP与哮喘和IgE相关。
ITGB3可能在哮喘和过敏的发生中起重要作用,可能代表治疗这些疾病的一个潜在治疗靶点。