G protein-coupled receptor 154 gene polymorphism is associated with airway hyperresponsiveness to methacholine in a Chinese population

J Allergy Clin Immunol. 2006 Mar;117(3):612-7. doi: 10.1016/j.jaci.2005.11.045. Epub 2006 Feb 15.

Abstract

Background: A new asthma susceptibility gene, the G protein-coupled receptor for asthma susceptibility (GPRA, GPR154), has recently been identified and the association was replicated in 2 white populations, but not in a Korean population.

Objective: To test the association between GPR154 gene polymorphisms and airway responsiveness to methacholine in a Chinese population.

Methods: Eight single nucleotide polymorphisms (SNPs) in the GPR154 gene were genotyped in 451 cases and 232 controls in stage I. The association of 1 SNP, rs324981, was tested in an additional 264 case and 241 control subjects in stage II. Both single marker and haplotype associations were tested.

Results: In stage I, we found that airway hyperresponsiveness to methacholine was associated with 2 single SNPs, rs324981 and rs324987, but not with the haplotypes of GPR154. The minor allele homozygotes of rs324981 (AA) and rs324987 (TT) were at a significantly lower risk of hyperresponsiveness to methacholine with odds ratios of 0.59 (P=.02) and 0.56 (P=.01), respectively. In stage II, we found a similar trend of association between rs324981 and airway hyperresponsiveness (P=.09). In the pooled analysis, the odds ratio of the AA homozygote of rs324981 was 0.61 (P=.004). The permutation test resulted in a study-wide empirical P value of .023, which meant that the association remained significant after adjustment for multiple tests.

Conclusions: Our study supports a role of the GPR154 gene in asthma susceptibility and suggests that the AA homozygote of rs324981 is a protective factor for airway hyperresponsiveness to methacholine in a Chinese population.

Clinical implications: Our findings confirmed a role of GPR154 in the genetic susceptibility of asthma and suggest that GPR154 polymorphism should be taken into consideration to improve the assessment of an individual's risk of asthma.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Asians / genetics*
  • Asthma / genetics*
  • Asthma / physiopathology
  • Bronchial Hyperreactivity / genetics*
  • Bronchial Provocation Tests
  • Bronchoconstrictor Agents
  • Case-Control Studies
  • Child
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Male
  • Methacholine Chloride
  • Middle Aged
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Receptors, G-Protein-Coupled / genetics*

Substances

  • Bronchoconstrictor Agents
  • NPSR1 protein, human
  • Receptors, G-Protein-Coupled
  • Methacholine Chloride