白细胞介素-4 多态性、白细胞介素-4 受体基因与哮喘的关系。
Association between the polymorphisms of interleukin-4, the interleukin-4 receptor gene and asthma.
机构信息
Allergy Research Laboratory, Institute of Respiratory Diseases, Fudan University, Shanghai 200040, China.
出版信息
Chin Med J (Engl). 2013;126(15):2943-51.
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.
背景
白细胞介素 4（IL4）是参与多种过敏性疾病的最重要细胞因子之一，尤其是哮喘。许多遗传流行病学研究已经确定了白细胞介素 4 基因多态性和白细胞介素 4 受体（IL4R）与不同人群哮喘之间的关联。然而，这些研究一直存在不一致和不确定的情况。本研究旨在通过荟萃分析，使用无遗传模型的方法研究白细胞介素 4（IL-4）、IL-4R 的单核苷酸多态性（SNP）与哮喘风险之间的关联。
方法
采用无遗传模型的方法进行荟萃分析。分别对哮喘（非特应性状态未定义）、非特应性和特应性哮喘亚组进行分析。然后，分析了种族亚组。还探索了异质性和发表偏倚。
结果
仅纳入了白细胞介素 4（rs2243250 和 rs2070874）和白细胞介素 4R（rs1801275、rs1805011、rs1805010 和 rs1805015）的两个 SNP 进行荟萃分析。白细胞介素 4 的 rs2243250 和 rs2070874 以及白细胞介素 4R 的 rs1801275 和 rs1805011 与哮喘相关。rs2243250 在 CC 与 TT+TC 基因型中的总体比值比（OR）为 0.84（95%CI：0.75-0.94），总体效应的 Z 检验值为 3.0（P=0.003）。我们在白人和成年人群中得到了该 SNP 的显著结果。然而，rs1801275 在 GG+AG 与 AA 基因型中的总体 OR 为 1.16（95%CI：1.00-1.35），总体效应的 Z 检验值为 1.87（P=0.06）。此外，仅在亚洲人群的亚组分析中得到了显著结果（P=0.02）。在白细胞介素 4R 的 rs1805011 多态性中，CC+AC 与 AA 基因型的总体 OR 为 0.39（95%CI：0.16-0.95），总体效应的 Z 检验值为 2.08（P=0.04）。
结论
白细胞介素 4 和白细胞介素 4R 的多态性均与哮喘相关。白细胞介素 4 的 rs2243250 多态性在白人和成年人群中更为重要。与 TT 纯合子相比，携带 IL4 基因 rs2070874 等位基因 C 的个体患哮喘的风险增加。与其他两种基因型相比，IL4R 基因 rs1805011 的 AA 基因型个体患哮喘的可能性较低。
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