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

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.

• Authors: Yan Feng, Xiumei Hong, Lin Wang, Shanqun Jiang, Changzhong Chen, Binyan Wang, Jianhua Yang, Zhian Fang, Tonghua Zang, Xiping Xu, Xin Xu
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 117 Issue 3 Pg. 612-7 (Mar 2006) ISSN: 0091-6749 [Print] United States
• PMID: 16522461 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

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

Topics

• Adolescent
• Adult
• Asian People (genetics)
• Asthma (genetics, 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)