title: IL-4 receptor alpha single-nucleotide polymorphisms rs1805010 and rs1801275 are associated with increased risk of asthma in a Saudi Arabian population.
abstract: BACKGROUND
  The IL-4 receptor alpha subunit (IL-4Rα), when associated with the common gamma chain receptor, or the IL-13Rα1 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-4Rα 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-4Rα rs1805010 and rs1801275 polymorphisms are associated with asthma in patients from Saudi Arabia.
  
  
  METHODS
  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-4Rα gene was performed by PCR amplification, followed by cycle sequencing of the purified PCR fragments using BigDye chain terminator and capillary electrophoresis.
  
  
  RESULTS
  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*).
  
  
  CONCLUSIONS
  The risk alleles, G, of IL-4Rα rs1805010 and rs1801275 SNPs and corresponding A/G-G/G genotypes were significantly associated with asthma predisposition in asthmatics from Saudi Arabia.
authors.affiliation: Prince Naif Center for Immunology Research, College of Medicine, King Saud University, Riyadh, Saudi Arabia ; Department of Paediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Saleh
authors.initials: S
authors.lastname: Al-Muhsen
authors.affiliation: Prince Naif Center for Immunology Research, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Vazquez-Tello
authors.affiliation: Zayed Military Hospital, Abu Dhabi, UAE.
authors.forename: Ashraf
authors.initials: A
authors.lastname: Alzaabi
authors.affiliation: Department of Internal Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Mohamed S
authors.initials: MS
authors.lastname: Al-Hajjaj
authors.affiliation: King Saud University for Health Sciences, Riyadh, Saudi Arabia.
authors.forename: Hamdan H
authors.initials: HH
authors.lastname: Al-Jahdali
authors.affiliation: Prince Naif Center for Immunology Research, College of Medicine, King Saud University, Riyadh, Saudi Arabia ; Department of Paediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Rabih
authors.initials: R
authors.lastname: Halwani
keywords: Asthma; IL-4 receptor alpha; STAT6; allergy; association; genotype; susceptibility