Association of single nucleotide polymorphisms on Interleukin 17 receptor A (IL17RA) gene with aspirin hypersensitivity in asthmatics

Abstract

To investigate the association of single nucleotide polymorphisms (SNP) on IL17RA gene with Aspirin Exacerbated Respiratory Disease (AERD) and the functional effect of these variants on expression of IL17RA gene products. 15 SNPs of IL17RA gene were analyzed in 825 normal controls and 143 subjects with AERD and 411 with aspirin-tolerant asthma (ATA) and functionally characterized using measurement of protein and m-RNA expression. Minor alleles frequencies of the three SNPs (-1075 A>G, -947 A>G, -50 C>T) and one haplotype (BL1_ht1) were significantly lower in AERD compared to those in ATA (p(corr)=0.002-0.03). IL17RA protein expression and mRNA amount in CD14(+) peripheral blood monocytes and mononuclear cells were significantly increased in subjects carrying the common alleles homozygote compared with those carrying the minor alleles. The minor alleles of the three SNPs may decrease the risk of AERD via attenuation of IL17RA gene expression.