Association between Interleukin-4 Receptor α Chain (IL4RA) I50V and Q551R Polymorphisms and Asthma Risk: An Update Meta-Analysis

Abstract

BackgroundThe associations between the interleukin-4 receptor α chain (IL4RA) I50V and Q551R polymorphisms and asthma risk remained controversial.MethodsWe searched the Pubmed, Embase, Chinese National Knowledge Infrastructure (CNKI) and Wanfang databases for studies published before February 2013. The strengths of the associations were calculated using odds ratios (ORs) with 95% confidence intervals (CIs).ResultsA total of 50 studies were included in this meta-analysis. There was a significant association between the IL4RA I50V polymorphism and asthma risk in a dominant genetic model (OR = 1.13, 95% CI 1.04–1.23, P = 0.005). The IL4RA Q551R polymorphism was associated with a significantly elevated asthma risk in a recessive genetic model (OR = 1.46, 95% CI 1.22–1.75, P<0.0001). Subgroup analyses found that the IL4RA I50V polymorphism was significantly associated with asthma risk in Asians (OR = 1.72, 95% CI 1.31–2.25, P<0.0001), pediatric asthma risk (OR = 1.50, 95% CI 1.13–1.99, P = 0.005), and atopic asthma risk (OR = 1.88, 95% CI 1.27–2.79, P = 0.002).ConclusionsThe results of this meta-analysis suggested that the IL4RA I50V and Q551R polymorphisms may be risk factors for developing asthma.

Single Nucleotide Polymorphism of IL4C-590T and IL4RA 175V and Immunological Parameters in Egyptian Asthmatics with Different Clinical Phenotypes

“…This could suggest that the patient carrying the A allele of IL-4RA-175V had an increased risk for asthma. This data is consistent with previous studies [24,26]. Nevertheless, other studies showed insignificant association of this polymorphism with asthma risk [18].…”

“…Previous reports have shown that IL-4 C-589T polymorphism influences asthma risk in a most probable dominant model, i.e., one -589T allele has adequate capacity to enhance the asthma risk of susceptible individuals [23]. Also, a previous meta-analysis observed the association between −589C/T polymorphism and asthma among Asians and Caucasians but not among African Americans [26]. Our results go hand in hand with this trend.…”

Identification of IL13 C1923T as a Single Nucleotide Polymorphism for Asthma in Children from Mauritius

“…17 that IL4RA Q551R polymorphism predisposes children but not adults to asthma, and its exact role in the pathogenesis is still not conclusive. 18 …”

Polymorphisms in the interleukin 4, interleukin 4 receptor and interleukin 13 genes and allergic phenotype: A case control study

“…Both interleukin 4 (IL4) and interleukin 13 (IL13) are cytokines produced mainly by T-helper 2 (Th2) cells and they play a crucial role in the pathogenesis of allergic inflammation including allergic asthma [1,2]. Interleukin 4 and interleukin 13 recruit mast cells and eosinophils, induce isotype class-switching of B-cells for IgE synthesis and regulate expression of MHC II, CD23 and VCAM-1 [3][4][5].…”

“…In regard to interleukin 4 receptor a chain gene, two functional polymorphisms were reported: rs1805010, observed to cause up-regulation of IL4Ra response to IL4 [17], and rs1805011, which function remains unknown. The former genetic variant was found to be associated with asthma [2,18] and the latter with asthma [14] and atopic dermatitis [19]. In interleukin 13 gene, a functional SNP contributing to aminoacid substitution R110Q (rs20541) was described to change the binding strength of IL13 to its receptor, causing higher activity of Gln110 variant [20].…”