Influence of Polymorphisms in the <b><i>Interleukin-18</i></b> Gene on Allergic Rhinitis: A Meta-Analysis

Abstract

Purpose: Reported associations of interleukin-18 (IL-18) single-nucleotide polymorphisms (SNPs) with allergic rhinitis (AR) have been inconsistent, prompting a meta-analysis to obtain more precise estimates. Methods: We synthesized data from 8 articles and examined 3 IL-18 SNPs. Two SNPs (rs360721 and rs187238), in linkage disequilibrium, were combined and termed RS1. The rs1946518 SNP was analyzed separately (termed RS2). The recessive, dominant, and codominant (multiplicative) genetic models were used to estimate ORs and 95% CIs. Subgroup analysis was ethnicitybased. Sources of heterogeneity were investigated with outlier treatment. Sensitivity analysis was used to assess robustness of the associative effects. Multiple comparisons were Holm-Bonferroni corrected. Results: All significant (p a < 0.05) outcomes indicating increased risks were found in the dominant/codominant models in RS1 and RS2. Five aspects of differences marked the significant African (RS1) and overall (RS2) outcomes: (i) magnitude of effect (ORs): greater (3.01-5.15) versus less (1.20-1.47); (ii) precision of effects (95% CIs): less (1.07-21.52) versus more (1.01-1.89); (iii) outlier treated: no versus yes; (iv) sensitivity outcomes: nonrobust versus robust (dominant model only); and (v) greater evidential strength for RS2 (p a = 0.002) compared to RS1 (p a = 0.02) rendered RS2 our core finding. These levels of statistical significance for RS1/RS2 enabled both to survive the Holm-Bonferroni correction. Conclusions: The core outcome indicating a 1.5-fold increased risk could render the IL-18 polymorphisms useful in the clinical genetics of AR. Future studies that could focus on other IL-18 SNPs may find deeper associations with AR than what we found here.

The Assessment of TLR1 Gene Polymorphism Association with the Risk of Allergic Rhinitis in the Chinese Han Population from Northern China

“…7,8 Numerous investigations have indicated that SNPs in ADAM33, IL-18, FOXP3, and IL13 have been implicated in susceptibility to AR. [9][10][11] Toll-like receptor 1 (TLR1) belongs to the TLR receptor family which plays a fundamental role in the activation of innate immunity. It has been reported that TLRs are involved in the pathogenesis of AR.…”

Allergens elicit upregulated IL‐18 and IL‐18Rα expression in blood monocytes of patients with allergic rhinitis

“…5 A pathologic role for IL-18 in the induction of allergic diseases includes stimulating mast cell and basophil degranulation 6 and activating basophils through pathways involving Syk and IκB kinases. 7 It is reported that the polymorphism of the IL-18 gene was associated with allergic rhinitis (AR), 8,9 and elevated IL-18 levels have been found in both the nasal secretion and serum of AR patients [10][11][12] and in the adenoid tissue of children with adenoid hypertrophy and coexistent AR. 13 It is also observed that elevated serum IL-18 levels, caused by natural pollen exposure, are closely associated with bronchial hyperresponsiveness in seasonal AR (sAR) patients.…”

Genetic Variations in Nucleotide Excision Repair Pathway Genes and Risk of Allergic Rhinitis

“…Numerous genetic studies suggested that single nucleotide polymorphisms (SNPs) in the key genes involved in the pathogenesis of AR contribute greatly to AR susceptibility, which can be classified as interleukin, chemokines, and their corresponding receptors [16,17]. The SNPs in the interleukin such as IL4 [18], IL6 [8], IL13 [19], IL18 [20], and IL33 [9] have been reported associated with the risk of AR, which are the key regulators in the progression of AR.…”