A Genetic Variation in Inositol Polyphosphate 4 Phosphatase A Enhances Susceptibility to Asthma

Rationale: Microarray data from mouse studies have identified a number of genes to be differentially expressed in allergen-sensitized mice lungs.Objectives: Taking leads from these datasets, we attempted to identify novel genes associated with atopic asthma in humans.Methods: We performed family-based genetic association analysis on selected markers within or in proximity of 21 human homologs of genes short-listed from ovalbumin-sensitized mouse studies in the Gene Expression Omnibus database of the National Center for Biotechnology Information. Family-based and case-control studies were undertaken for fine mapping and functional variation analysis of INPP4A (inositol polyphosphate 4 phosphatase type I). Western blot analysis was performed to analyze INPP4A protein stability from human platelets.Measurements and Main Results: Our genetic association studies of 21 human genes in 171 trios led to the identification of a biallelic repeat (rs3217304) in INPP4A, associated with atopic asthma (P = 0.009). Furth...