Dataset Information

Polymorphisms in Human IL4, IL10, and TNF Genes Are Associated with an Increased Risk of Developing NSAID-Exacerbated Respiratory Disease.

ABSTRACT:

Background

The role of genetics in non-steroidal anti-inflammatory drugs (NSAID) exacerbated respiratory disease (NERD) is unclear, with different candidates involved, such as HLA genes, genes related to leukotriene synthesis, and cytokine genes. This study aimed to determine possible associations between 22 polymorphisms in 13 cytokine genes.

Methods

We included 195 patients (85 with NERD and 110 with respiratory disease who tolerate NSAIDs) and 156 controls (non-atopic individuals without a history of asthma, nasal polyposis (NP), or NSAID hypersensitivity). Genotyping was performed by sequence-specific primer polymerase chain reaction (PCR-SSP). Amplicons were analyzed by horizontal gel electrophoresis in 2% agarose.

Results

Significant differences in allele and genotype frequency distributions were found in TNF (rs1800629), IL4 (rs2243248 and rs2243250), and IL10 (rs1800896, rs1800871, and rs1800872) genes in patients with NSAID hypersensitivity. In all cases, the minor allele and the heterozygous genotype were more prevalent in NERD. An association of TNF rs1800629 SNP with respiratory disease in NSAID-tolerant patients was also found.

Conclusions

Retrospectively recorded, we found strong associations of NERD with polymorphisms in IL4, IL10, and TNF genes, suggesting that these genes could be involved in the inflammatory mechanisms underlying NERD.

SUBMITTER: Reigada-Rivera ML

PROVIDER: S-EPMC9031626 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Publications

Polymorphisms in Human <i>IL4</i>, <i>IL10</i>, and <i>TNF</i> Genes Are Associated with an Increased Risk of Developing NSAID-Exacerbated Respiratory Disease.

Reigada-Rivera María Luisa ML Lozano Catalina Sanz CS Rodilla Esther Moreno EM García-Sánchez Asunción A García-Solaesa Virginia V Toledano Félix Lorente FL González Ignacio Dávila ID Isidoro-García María M

Genes 20220328 4

<h4>Background</h4>The role of genetics in non-steroidal anti-inflammatory drugs (NSAID) exacerbated respiratory disease (NERD) is unclear, with different candidates involved, such as <i>HLA</i> genes, genes related to leukotriene synthesis, and cytokine genes. This study aimed to determine possible associations between 22 polymorphisms in 13 cytokine genes.<h4>Methods</h4>We included 195 patients (85 with NERD and 110 with respiratory disease who tolerate NSAIDs) and 156 controls (non-atopic in ...[more]

PMID: 35456412

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Project description:Nonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (N-ERD) is a clinical syndrome characterized by nasal polyposis, asthma, and intolerance to aspirin/NSAID. It affects approximately 15% cases of severe asthma, 10% of nasal polyps and 9% of rhinosinusitis. N-ERD results in associated asthma exacerbations, oral corticosteroids bursts, corticosteroid-dependent disease, and multiple endoscopic sinus surgeries. Unknown influences cause polyp epithelium to release alarmins, such as IL-33 and TSLP. These cytokines activate lymphoid cells, both Th2 and ILC2, to release cytokines such as IL5, IL4 and IL13, resulting in complex type 2 inflammation involving mast cells, eosinophils and platelets. Arachidonic acid released from such cells is metabolized into mediators. N-ERD is characterized by an imbalance in eicosanoid levels, especially CysLTs, PDG and PGE2. Patients with N-ERD present nasal symptoms (congestion, hyposmia/anosmia, nasal discharge) and lower airways symptoms (cough, sneezing, shortness of breath, chest tightness), anosmia, severe hyposmia as well as severe asthma which impacts the quality of life in this disease and leads to safety concerns in patients daily lives. Despite the variety of treatment strategies, the likelihood of recurrence of symptoms is high in patients with N-ERD. The most important strategies for treating N-ERD are listed as following: drug therapies, aspirin desensitization, monoclonal antibodies and other therapies associated. N-ERD treatment remains a major challenge in the current situation. Selecting the appropriate patient for aspirin desensitization, monoclonal antibodies or both is essential. This review provides an overview on aspirin desensitization and biologics in N-ERD and might help in decision making from both the perspective of the physician and patient. Patient characteristics, safety, efficacy, health care costs, but also patient preferences are all factors to take into account when it comes to a choice between biologics or aspirin desensitization.