Genetic variants in PD-1 and its ligands, gene-gene and gene-environment interactions in allergic rhinitis.

Background: The etiology of allergic rhinitis (AR), in which genetic and environmental factors are closely intertwined, has not yet been completely clarified. Programmed cell death 1 (PD-1) and its ligands (PD-L1 and PD-L2) regulate the immune and inflammatory responses during the development of immune-related and atopic diseases. To clarify the associations of genetic variants in PD-1, PD-L1 and PD-L2 with susceptibility to AR, gene-gene and gene-environment interactions were investigated.

Methods: A total of 452 AR patients and 495 controls were enrolled in this hospital-based case-control study. Eight single nucleotide polymorphisms (SNPs) in the PDCD1, PDCD1LG1 and PDCD1LG2 genes were genotyped. The correlations between SNPs and AR incidence, as well as gene-gene and gene-environment interactions were explored. Differentially expressed genes were screened by the Limma package in two Gene Expression Omnibus (GEO) datasets of AR patients. Expression qualitative trait locus (eQTL) analysis was performed via the Genotype-Tissue Expression (GTEx) database.

Results: The rs2297136 (A/G) in PDCD1LG1 was associated with a significantly increased risk of AR, whereas the PDCD1LG2 rs16923189 G allele was associated with a reduced risk of AR. In the subgroups according to AR-related phenotypes, the rs2297136 G allele increased, while the rs16923189 G allele reduced AR risk. Gene-gene interactions and gene-environment interactions (e.g., PDCD1LG1 polymorphisms with factors such as smoke, main road and cooking fumes) were verified in AR patients, but they were not significant after Bonferroni correction.

Conclusion: PDCD1LG1 rs2297136 and PDCD1LG2 rs16923189 are associated with susceptibility to AR in this Chinese population. The PD-1/PD-L1 and PD-1/PD-L2 signaling pathways may regulate gene-gene and gene-environment interactions in the pathogenesis of AR.