IL-4 receptor alpha single-nucleotide polymorphisms rs1805010 and rs1801275 are associated with increased risk of asthma in a Saudi Arabian population

ABSTRACT

The IL-4 receptor alpha subunit [IL-4Ralpha], when associated with the common gamma chain receptor, or the IL-13Ralpha1 subunit, transduces signals to STAT6 in response to IL-4 and IL-13 stimulations. This results in a number of cell-specific responses including Th2 differentiation, lymphocyte proliferation and IgE production. Given the prominent role of IL-4Ralpha in allergic disorders, several single-nucleotide polymorphisms [SNPs] have been found associated with asthma and other atopic disorders, including rs1805010 [I75V] and rs1801275 [Q576R] SNPs; however, lack of significant association have also been reported for some ethnic groups. The objective of this study was to determine whether IL-4Ralpha rs1805010 and rs1801275 polymorphisms are associated with asthma in patients from Saudi Arabia. One hundred and ninety severe asthmatic patients [11-70 years old] and 194 healthy subjects of equivalent age range were recruited for blood donation. DNA was purified and genotyping for rs1801275 and rs1805010 polymorphisms in the IL-4Ralpha gene was performed by PCR amplification, followed by cycle sequencing of the purified PCR fragments using BigDye chain terminator and capillary electrophoresis. Pearson's Chi-square tests showed that the minor alleles, G, for both rs1805010 and rs1801275 SNPs, were significantly more frequent in asthmatics than in the healthy group [Yates' P < 0.05]; conversely, the major alleles, A, were significantly more frequent in healthy than in asthmatics [P < 0.05]. Concerning association analysis, odds for A/G-G/G genotypes were significantly higher to be associated with asthma predisposition [rs1801275 OR = 2.12; 95% CI = 1.39-3.22; P < 0.001*; rs1805010 OR = 1.6; 95% CI = 1.01-2.53; P < 0.05*; dominant model]. Analysis of gender-genotype interactions, with genders nested within A/G-G/G, indicated higher odds for females than males of significant association with asthma [rs1801275 OR = 5.19, 95% CI = 2.09-12.94*; rs1805010 OR = 3.73, 95% CI = 2.06-6.74*]. Rs1805010 and rs1801275 were in linkage disequilibrium [D' = 0.27; P < 0.0004*], with G-G haplotype being more frequent in asthmatics than in healthy subjects [OR = 2.43, 95% CI = 1.59-3.71*].The risk alleles, G, of IL-4Ralpha rs1805010 and rs1801275 SNPs and corresponding A/G-G/G genotypes were significantly associated with asthma predisposition in asthmatics from Saudi Arabia.