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. 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.
journal_name
Ann Thorac Medjournal_title
Annals of thoracic medicineauthors
Al-Muhsen S,Vazquez-Tello A,Alzaabi A,Al-Hajjaj MS,Al-Jahdali HH,Halwani Rdoi
10.4103/1817-1737.128849subject
Has Abstractpub_date
2014-04-01 00:00:00pages
81-6issue
2eissn
1817-1737issn
1998-3557pii
ATM-9-81journal_volume
9pub_type
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journal_title:Annals of thoracic medicine
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doi:10.4103/1817-1737.33702
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journal_title:Annals of thoracic medicine
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journal_title:Annals of thoracic medicine
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doi:10.4103/1817-1737.44783
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pub_type: 杂志文章
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journal_title:Annals of thoracic medicine
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journal_title:Annals of thoracic medicine
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pub_type: 杂志文章,评审
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pub_type: 杂志文章
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pub_type: 已发布勘误
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pub_type: 杂志文章,评审
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pub_type: 杂志文章
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journal_title:Annals of thoracic medicine
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journal_title:Annals of thoracic medicine
pub_type: 杂志文章
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journal_title:Annals of thoracic medicine
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journal_title:Annals of thoracic medicine
pub_type: 杂志文章
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journal_title:Annals of thoracic medicine
pub_type:
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pub_type: 杂志文章
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pub_type: 杂志文章
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