Abstract
ObjectiveInterleukin-1 receptor-associated kinase-4 (IRAK-4) encodes a kinase that is essential for NF-kB activation in Toll-like receptor and T-cell receptor signaling pathways, indicating a possible crosstalk between innate and acquired immunities. We attempted to determine whether the polymorphisms in the Interleukin-1 receptor-associated kinase-4 (IRAK-4) gene are associated with allergic rhinitis (AR) in the Han Chinese population.MethodsA population of 379 patients with AR and 333 healthy controls was studied. Blood was drawn for DNA extraction and total serum immunoglobulin E (IgE). A total of 11 single nucleotide polymorphisms (SNPs) in IRAK-4 were selected and individually genotyped.ResultsSignificant allelic differences between cases and controls were obtained for the SNP of rs3794262 in the IRAK-4 gene. In the stratified analysis for gender, two SNPs (rs4251431 and rs6582484) in males appeared as significant associations. Subgroup analysis for the presence of different allergen sensitivities displayed associations only in the house dust mite-allergic cohorts (rs3794262, rs4251481). None of the selected SNPs in IRAK-4 was associated with total IgE level. The haplotype analyisis indicated GCCTGCGA was significantly associated with AR. The SNP-SNP interaction information analysis indicated that the selected sets of polymorphisms had no synergistic effect.ConclusionsOur findings did not support the potential contribution of the IRAK-4 gene to serum IgE levels. However, the results demonstrated a gender- and allergen-dependant association pattern between polymorphisms in IRAK-4 and AR in Chinese population.
Highlights
Allergic rhinitis (AR) is an inflammatory disease of the nasal mucosa induced by an immunoglobulin E (IgE)-mediated reaction in allergen-sensitized subjects
The cohort of 379 allergic rhinitis (AR) patients had a mean age of 27 years and consisted of more men (59.9%) than women (40.1%), while the 333 control individuals had a mean age of 36 years and a similar component of more men (53.8%) than women (46.2%)
Patients were diagnosed as having AR by combining the skin test and serum specific IgE data with the allergen-specific case history and nasal physical examination. 73.9% of individuals demonstrated perennial nasal symptoms while the remainder reported seasonally-related reactions
Summary
Allergic rhinitis (AR) is an inflammatory disease of the nasal mucosa induced by an immunoglobulin E (IgE)-mediated reaction in allergen-sensitized subjects. Recent data on self-reported AR in the centre of cities across mainland China demonstrated a prevalence of 8.7%– 24.1% [2] This high prevalence translates into a high cost to society in terms of overall healthcare use and the quality of life of those with moderate-to-severe disease. AR has multifactorial inheritance, and it is likely that different combinations of genes or single nucleotide polymorphisms (SNPs) increase the risk of phenotypic expression, resulting in allergic inflammation. Another explanation is proposed in the hygiene hypothesis, which suggests that as a result of modern public health practices, individuals encounter a reduced microbial burden, rendering them vulnerable to the development of allergic disease [3]
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