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

• Published in: Journal of allergy and clinical immunology Vol. 127; no. 6; pp. 1457 - 1465
• Main Authors: Li, Xingnan, Howard, Timothy D., Moore, Wendy C., Ampleford, Elizabeth J., Li, Huashi, Busse, William W., Calhoun, William J., Castro, Mario, Chung, Kian Fan, Erzurum, Serpil C., Fitzpatrick, Anne M., Gaston, Benjamin, Israel, Elliot, Jarjour, Nizar N., Teague, W. Gerald, Wenzel, Sally E., Peters, Stephen P., Hawkins, Gregory A., Bleecker, Eugene R., Meyers, Deborah A.
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.06.2011; Elsevier; Elsevier Limited
• Subjects: African Americans; Allergy and Immunology; Asthma; Asthma - genetics; Asthma - physiopathology; asthma severity; Biological and medical sciences; Black or African American - genetics; Bronchial Hyperreactivity - genetics; bronchodilators; Carrier Proteins - genetics; chromosomes; Chronic obstructive pulmonary disease, asthma; FAM13A; FEV 1; FEV 1/FVC; Fundamental and applied biological sciences. Psychology; Fundamental immunology; FVC; Genealogy; Genes; Genetic Predisposition to Disease; genetics; Genome-Wide Association Study; HHIP; Hispanic people; Humans; Hypotheses; Immunopathology; Linkage Disequilibrium; lung function; Medical sciences; Membrane Glycoproteins - genetics; Meta-analysis; Patched Receptors; Patched-1 Receptor; Pneumology; Polymorphism, Single Nucleotide; Population; Proto-Oncogene Proteins - genetics; PTCH1; Receptor, Notch4; Receptors, Cell Surface - genetics; Receptors, Notch - genetics; Respiratory Function Tests; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; sequence homology; single nucleotide polymorphism; Studies; Thrombospondins - genetics; White People - genetics; ATS; pp; TENOR; GWAS; HHIP; PTCH1; FAM13A; meta-analysis; SARP; asthma severity; Asthma; FEV 1/FVC; FVC; genetics; FEV 1; SNP; CSGA; LD; COPD; Forced vital capacity; Linkage disequilibrium; Genome-wide association study; Patched homolog 1; Chronic obstructive pulmonary disease; Family with sequence similarity 13, member A; Collaborative Studies on the Genetics of Asthma; Percent predicted; American Thoracic Society; Severe Asthma Research Program; The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens; Hedgehog interacting protein; Single nucleotide polymorphism; Lung disease; Immunopathology; Respiratory disease; Metaanalysis; Lung function; Immunology; Gene; Hedgehog protein; FEV; FEV1/FVC; Bronchus disease; Genetics; Obstructive pulmonary disease
• ISSN: 0091-6749; 1097-6825; 1097-6825
• DOI: 10.1016/j.jaci.2011.01.056

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. 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. 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. 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. 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.