A genetic variation in inositol polyphosphate 4 phosphatase a enhances susceptibility to asthma

American Journal of Respiratory and Critical Care Medicine
Mamta SharmaBalaram Ghosh

Abstract

Microarray data from mouse studies have identified a number of genes to be differentially expressed in allergen-sensitized mice lungs. Taking leads from these datasets, we attempted to identify novel genes associated with atopic asthma in humans. 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. 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). Further studies using additional three single nucleotide polymorphisms (SNPs), +92031A/T, +92344C/T, and +131237C/T, and two microsatellite markers, D2S2311 and D2S2187, revealed significant genetic associations with loci +92031A/T (P = 0.0012) and +92344C/T (P = 0.004). A nonsynonymous SNP,...Continue Reading

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Citations

May 9, 2009·American Journal of Respiratory and Critical Care Medicine·Wendy C Moore
Jul 27, 2010·American Journal of Respiratory Cell and Molecular Biology·Anurag AgrawalBalaram Ghosh
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Jul 4, 2021·Advances in Biological Regulation·Sabryn A HamilaChristina A Mitchell

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