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

BACKGROUND

The role of genetics in non-steroidal anti-inflammatory drugs (NSAID) exacerbated respiratory disease (NERD) is unclear, with different candidates involved, such as 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 (rs1800629), (rs2243248 and rs2243250), and (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 rs1800629 SNP with respiratory disease in NSAID-tolerant patients was also found.

CONCLUSIONS

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