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.
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.
Authors: Lisa J Martin; Hua He; Margaret H Collins; J Pablo Abonia; Joceyln M Biagini Myers; Michael Eby; Hanna Johansson; Leah C Kottyan; Gurjit K Khurana Hershey; Marc E Rothenberg Journal: J Allergy Clin Immunol Date: 2017-11-10 Impact factor: 10.793