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

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 I SNP, rs324981, was tested in an additional 264 case and 241 control subjects in stage If. 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.