Chinese Medical Journal 2013;126(15):2943-2951
Keywords
interleukin-4; interleukin-4 receptor; asthma; gene polymorphism; case-controlled study; meta-analysis
Abstract
Background Interleukin-4 (IL4) is one of the most important cytokines involved in a variety of
allergic disorders, particularly, asthma. A number of genetic epidemiological studies have identified
an association between the gene polymorphisms of IL4 and interleukin-4 receptor (IL4R) and asthma
in different populations. However, these studies have been inconsistent and inconclusive. The aim of this
study was to investigate the association between the single nucleotide polymorphism (SNP) of IL-4,
IL-4R and asthma risk in case-controlled studies using meta-analysis.
Method A genetic model-free approach was used to perform the meta-analysis. Asthma (atopy status
nondefined), nonatopic and atopic asthma subgroups were separately analyzed. Next, the ethnic
subgroup was analyzed. Heterogeneity and publication bias were also explored.
Results Only two polymorphisms of IL4 (rs2243250 and rs2070874) and four polymorphisms of
IL4R (rs1801275, rs1805011, rs1805010, and rs1805015) were included in the meta-analysis.
Polymorphisms rs2243250 and rs2070874 of IL-4 and rs1801275 and rs1805011 of IL4R were associated
with asthma. The overall odds ratio (OR) of rs2243250 in the CC versus TT+TC genotypes was 0.84
(95% CI: 0.75–0.94), and the Z-test for the overall effect was 3.0 (P=0.003). We obtained significant
results from this polymorphism in the Caucasian ethnicity and adult groups. However, the overall OR of
rs1801275 for the GG+AG versus AA genotype was 1.16 (95% CI: 1.00–1.35), and the Z-test for the
overall effect was 1.87 (P=0.06). Moreover, significant results were only obtained from the sub-group
analysis in Asians (P=0.02). In the rs1805011 polymorphism of IL4R, the overall OR for the CC +AC versus
AA genotypes was 0.39 (95% CI: 0.16–0.95), and the Z-test for the overall effect was 2.08 (P=0.04).
Conclusions
Both the IL4 and IL4R polymorphisms were associated with asthma. The rs2243250 polymorphism of IL4
was more important in the white and adult groups. Individuals who carried the C allele for rs2070874 of the
IL4 gene demonstrated increased asthma risk compared to TT homozygotes. An individual with an AA
genotype in rs1805011 of the IL4R gene was less likely to suffer from asthma compared to the other two
genotypes.
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