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

J Allergy Clin Immunol. 2011 Jun;127(6):1457-65. doi: 10.1016/j.jaci.2011.01.056. Epub 2011 Mar 12.


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.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asthma / genetics*
  • Asthma / physiopathology
  • Black or African American / genetics
  • Bronchial Hyperreactivity / genetics
  • Carrier Proteins / genetics*
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • Linkage Disequilibrium
  • Membrane Glycoproteins / genetics*
  • Patched Receptors
  • Patched-1 Receptor
  • Polymorphism, Single Nucleotide*
  • Proto-Oncogene Proteins / genetics
  • Receptor, Notch4
  • Receptors, Cell Surface / genetics
  • Receptors, Notch / genetics
  • Respiratory Function Tests
  • Thrombospondins / genetics
  • White People / genetics


  • Carrier Proteins
  • HHIP protein, human
  • Membrane Glycoproteins
  • NOTCH4 protein, human
  • PID1 protein, human
  • PTCH1 protein, human
  • Patched Receptors
  • Patched-1 Receptor
  • Proto-Oncogene Proteins
  • Receptor, Notch4
  • Receptors, Cell Surface
  • Receptors, Notch
  • Thrombospondins

Grant support