出生顺序修饰了 IL13 基因多态性对 10 岁时血清 IgE 和 4、10、18 岁时皮肤点刺试验的影响：一项前瞻性出生队列研究。
Birth order modifies the effect of IL13 gene polymorphisms on serum IgE at age 10 and skin prick test at ages 4, 10 and 18: a prospective birth cohort study.
机构信息
Department of Epidemiology and Biostatistics, Norman J Arnold School of Public Health, University of South Carolina, USA.
出版信息
Allergy Asthma Clin Immunol. 2010 Apr 20;6(1):6. doi: 10.1186/1710-1492-6-6.
BACKGROUND
Susceptibility to atopy originates from effects of the environment on genes. Birth order has been identified as a risk factor for atopy and evidence for some candidate genes has been accumulated; however no study has yet assessed a birth order-gene interaction.
OBJECTIVE
To investigate the interaction of IL13 polymorphisms with birth order on allergic sensitization at ages 4, 10 and 18 years.
METHODS
Mother-infant dyads were recruited antenatally and followed prospectively to age 18 years. Questionnaire data (at birth, age 4, 10, 18); skin prick test (SPT) at ages 4, 10, 18; total serum IgE and specific inhalant screen at age 10; and genotyping for IL13 were collected. Three SNPs were selected from IL13: rs20541 (exon 4, nonsynonymous SNP), rs1800925 (promoter region) and rs2066960 (intron 1). Analysis included multivariable log-linear regression analyses using repeated measurements to estimate prevalence ratios (PRs).
RESULTS
Of the 1456 participants, birth order information was available for 83.2% (1212/1456); SPT was performed on 67.4% at age 4, 71.2% at age 10 and 58.0% at age 18. The prevalence of atopy (sensitization to one or more food or aeroallergens) increased from 19.7% at age 4, to 26.7% at 10 and 41.1% at age 18. Repeated measurement analysis indicated interaction between rs20541 and birth order on SPT. The stratified analyses demonstrated that the effect of IL13 on SPT was restricted only to first-born children (p = 0.007; adjusted PR = 1.35; 95%CI = 1.09, 1.69). Similar findings were noted for firstborns regarding elevated total serum IgE at age 10 (p = 0.007; PR = 1.73; 1.16, 2.57) and specific inhalant screen (p = 0.034; PR = 1.48; 1.03, 2.13).
CONCLUSIONS
This is the first study to show an interaction between birth order and IL13 polymorphisms on allergic sensitization. Future functional genetic research need to determine whether or not birth order is related to altered expression and methylation of the IL13 gene.
背景
特应性的易感性源于环境对基因的影响。出生顺序已被确定为特应性的危险因素，并且已经积累了一些候选基因的证据；然而，尚无研究评估出生顺序-基因相互作用。
目的
调查 IL13 多态性与出生顺序对 4、10 和 18 岁时过敏致敏的相互作用。
方法
在产前招募母婴对子，并进行前瞻性随访至 18 岁。收集问卷调查数据（出生时、4 岁、10 岁、18 岁）；4 岁、10 岁、18 岁时进行皮肤点刺试验（SPT）；10 岁时进行总血清 IgE 和特定吸入物筛查；并进行 IL13 基因分型。从 IL13 中选择了三个 SNP：rs20541（外显子 4，非同义 SNP）、rs1800925（启动子区域）和 rs2066960（内含子 1）。分析包括使用重复测量的多变量对数线性回归分析来估计患病率比（PR）。
结果
在 1456 名参与者中，有 83.2%（1212/1456）提供了出生顺序信息；在 4 岁时进行了 67.4%的 SPT，在 10 岁时进行了 71.2%的 SPT，在 18 岁时进行了 58.0%的 SPT。特应性（对一种或多种食物或空气过敏原的敏感性）的患病率从 4 岁时的 19.7%增加到 10 岁时的 26.7%，18 岁时的 41.1%。重复测量分析表明 rs20541 与出生顺序之间存在 SPT 相互作用。分层分析表明，IL13 对 SPT 的影响仅局限于第一胎儿童（p=0.007；调整后的 PR=1.35；95%CI=1.09,1.69）。在第一胎儿童中，10 岁时总血清 IgE 升高（p=0.007；PR=1.73；1.16,2.57）和特定吸入物筛查（p=0.034；PR=1.48；1.03,2.13）也有类似的发现。
结论
这是第一项表明出生顺序与 IL13 多态性之间存在过敏致敏相互作用的研究。未来的功能遗传研究需要确定出生顺序是否与 IL13 基因的表达和甲基化改变有关。
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