Gene Polymorphisms within STAT6 and IL-4R-α are associated with increased risk of asthma in a Saudi Arabian population

Background: IL-4Rα rs1805010 and rs1801275 SNPs have been found to be significantly associated with asthma susceptibility in different ethnic groups; some STAT6 SNPs, including rs324011 and rs324015, have also been associated with asthma predisposition and/or IgE levels. Risk evaluations of IL-4Rα and STAT6 SNPs in association with asthma have never been evaluated in Saudi Arabian populations. We investigated whether IL-4Rα (rs1805010 and rs1801275) and STAT6 (rs324011 and rs324015) polymorphisms are associated with asthma in a population of asthmatic patients from Saudi Arabia.

Methods: Saudi Arabian patients with documented history of severe asthma (n=320) and healthy subjects (n=350) were recruited. Allelic and genotype association to asthma was assessed for IL-4Rα and STAT6 polymorphisms using nucleotide sequencing.

Results: Genotype frequencies were analyzed by testing distinct genetic models, either adjusted or not for covariate gender. The IL4Rα rs1801275 SNP A/G-G/G genotypes, but not the A/A genotype, were significantly associated with asthma predisposition (OR=0.47; 95% CI=0.31-0.72; P<0.001*; dominant model); IL4Rα rs1805010 SNP was also significantly associated with asthma (OR=0.62; 95% CI=0.39-0.99; P=0.043*). Similarly, for STAT6 rs324011, odds were significantly higher that homozygous T/T genotype could be associated with asthma; contrariwise, STAT6 rs324015 genotypes were not significantly associated with asthma, according to this analysis (genotype A/A: OR=0.70, 95%CI=0.29-1.70, P-value=0.43; recessive model).

Conclusions: The minor allele, G, of IL-4Rα rs1805010 and rs1801275 SNPs, and the corresponding A/G and G/G genotypes were significantly associated with asthma predisposition in asthmatic patients from Saudi Arabia; STAT6 rs324011 T/T genotype was also significantly associated with asthma predisposition, whereas rs324015 genotypes were not.