Single nucleotide polymorphisms (SNPs) close to the gain-of-function substitution, Asn(107)Ile (rs324981, A>T), in Neuropeptide S Receptor 1 (NPSR1) have been associated with asthma.
Notably, this inhibition is absent in the asthma-linked N107I variant of NPSR, suggesting that residue 107 interacts with the aforementioned regulatory region of NPS.
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.
The most significant association with rs7164773 (T/C) was driven by the CC genotype in asthma cases (OR = 2.0, 95%CI 1.36-2.93, p = 0.0003 in BAMSE; and 1.61, 1.18-2.19, p = 0.002 in the combined BAMSE-PARSIFAL datasets, respectively), and strikingly, the risk effect was dependent on the Gln344Arg mutation in NPSR1.
Similarly, allele C of rs740347 conferred low risk for asthma (OR: 0.44; 95% CI: 0.28-0.70, P=0.00017; Pc=0.00037) and total IgE (OR: 0.29; 95% CI: 0.09-0.88, P=0.015; Pc=0.030) in the case-control study and families (Z score=-3.207, P=0.0013; Z score=-3.182, P=0.0014, respectively).