Annals of Thoracic Medicine Official publication of the Saudi Thoracic Society, affiliated to King Saud University
 
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ORIGINAL ARTICLE
Year : 2014  |  Volume : 9  |  Issue : 2  |  Page : 81-86

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


1 Prince Naif Center for Immunology Research; Department of Paediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia
2 Prince Naif Center for Immunology Research, College of Medicine, King Saud University, Riyadh, Saudi Arabia
3 Department of Paediatrics, Zayed Military Hospital, Abu Dhabi, United Arab Emirates
4 Department of Internal Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia
5 King Saud University for Health Sciences, Riyadh, Saudi Arabia

Correspondence Address:
Rabih Halwani
Prince Naif Center for Immunology Research, Asthma Research Chair, College of Medicine, King Saud University, P.O. Box 2925, Postal Code 11461, Riyadh
Saudi Arabia
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DOI: 10.4103/1817-1737.128849

PMID: 24791170

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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. Materials and 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.


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