Variation in ITGB3 is associated with asthma and sensitization to mold allergen in four populations

Rationale: Recent genetic studies have implicated integrins in asthma and atopy susceptibility. We therefore evaluated the integrin-beta 3 gene (ITGB3), an integrin gene within an asthma linkage peak on chromosome 17, as a candidate for susceptibility to asthma- and atopy-related phenotypes. Methods and Measurements: We genotyped and performed association tests on 19 single nucleotide polymorphisms in ITG83 in the Hutterites, a founder population, and in three outbred replication populations. Main Results: Variation in ITGB3 was strongly associated with susceptibility to bronchial hyperresponsiveness and protection from allergic sensitization to mold allergens in this population. Three independent case-control populations representing Caucasians and African Americans were used to replicate this finding, also revealing ITG83 alleles that are associated with asthma susceptibility and protection from mold allergen sensitization. Conclusions: This study provides evidence that ITGB3 plays a role in the pathogenesis of asthma and sensitization to mold allergens.