Importance of hedgehog interacting protein and other lung function genes in asthma.

TitleImportance of hedgehog interacting protein and other lung function genes in asthma.
Publication TypeJournal Article
Year of Publication2011
AuthorsLi X, Howard TD, Moore WC, Ampleford EJ, Li H, Busse WW, Calhoun WJ, Castro M, Chung K F, Erzurum SC, Fitzpatrick AM, Gaston B, Israel E, Jarjour NN, Teague GW, Wenzel SE, Peters SP, Hawkins GA, Bleecker ER, Meyers DA
JournalJ Allergy Clin Immunol
Volume127
Issue6
Pagination1457-65
Date Published2011 Jun
ISSN1097-6825
KeywordsAfrican Americans, Asthma, Bronchial Hyperreactivity, Carrier Proteins, European Continental Ancestry Group, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Linkage Disequilibrium, Membrane Glycoproteins, Polymorphism, Single Nucleotide, Proto-Oncogene Proteins, Receptors, Cell Surface, Receptors, Notch, Respiratory Function Tests, Thrombospondins
Abstract

BACKGROUND: Two recent large meta-analyses of genome-wide association studies of lung function in general populations of European descent identified 11 candidate genes/regions. The importance of these genes in lung function in white and African American subjects with asthma is unknown.

OBJECTIVES: To determine whether genes that regulate lung function in general populations are associated with lung function abnormalities in subjects with asthma from different racial groups.

METHODS: Single nucleotide polymorphisms (SNPs) were tested in 5 asthma populations (N = 1441) for association with pulmonary function, and meta-analysis was performed across populations. The SNPs with the highest significance were then tested for association with bronchodilator reversibility and bronchial hyperresponsiveness to methacholine. A joint analysis of consistently replicated SNPs was performed to predict lung function in asthma.

RESULTS: Hedgehog interacting protein (HHIP) on chromosome 4q31 was associated with lung function in all 5 populations (rs1512288: P(meta) = 9.62E-05 and 3.23E-05 for percent predicted FEV(1) [ppFEV(1)] and percent predicted forced vital capacity [ppFVC], respectively). The SNPs in HHIP were also associated with reversibility (P < .05) but not bronchial hyperresponsiveness to methacholine. Because of differences in linkage disequilibrium in the African American subjects, the most relevant SNPs in HHIP were identified. A subset of normal lung function genes, including HHIP, family with sequence similarity 13, member A (FAM13A), and patched homolog 1 (PTCH1), together predict lung function abnormalities, a measure of severity in white and African American subjects with asthma.

CONCLUSION: A subset of the genes, including HHIP, that regulate lung function in general populations are associated with abnormal lung function in asthma in non-Hispanic white and African American subjects.

DOI10.1016/j.jaci.2011.01.056
Alternate JournalJ. Allergy Clin. Immunol.
PubMed ID21397937

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