Ruo-Xi Chen , Zheng Luan , Chong Shen , Meng-Di Dai , Chang-Yu Qiu , Xin-Jie Zhu , Qing-Zhao Zhang , Mei-Ping Lu , Lei Cheng
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引用次数: 0
Abstract
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.
期刊介绍:
International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome.
The subject material appropriate for submission includes:
• Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders.
• Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state.
• Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses.
• Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action.
• Agents that activate genes or modify transcription and translation within the immune response.
• Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active.
• Production, function and regulation of cytokines and their receptors.
• Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.