Tsai H-J, Kumar R, Pongracic J, Liu X, Story R, Yu Y, Caruso D, Costello J, Schroeder A, Fang Y, Demirtas H, Meyer K E, O'Gorman M R G, Wang X
Mary Ann and J. Milburn Smith Child Health Research Program, Children's Memorial Hospital and Children's Memorial Research Center, Chicago, IL, USA.
Clin Exp Allergy. 2009 Jan;39(1):101-9. doi: 10.1111/j.1365-2222.2008.03111.x. Epub 2008 Oct 30.
The increasing prevalence of food allergy (FA) is a growing clinical and public health problem. The contribution of genetic factors to FA remains largely unknown.
This study examined the pattern of familial aggregation and the degree to which genetic factors contribute to FA and sensitization to food allergens.
This study included 581 nuclear families (2,004 subjects) as part of an ongoing FA study in Chicago, IL, USA. FA was defined by a set of criteria including timing, clinical symptoms obtained via standardized questionnaire interview and corroborative specific IgE cut-offs for > or =95% positive predictive value (PPV) for food allergens measured by Phadia ImmunoCAP. Familial aggregation of FA as well as sensitization to food allergens was examined using generalized estimating equation (GEE) models, with adjustment for important covariates including age, gender, ethnicity and birth order. Heritability was estimated for food-specific IgE measurements.
FA in the index child was a significant and independent predictor of FA in other siblings (OR=2.6, 95% CI: 1.2-5.6, P=0.01). There were significant and positive associations among family members (father-offspring, mother-offspring, index-other siblings) for total IgE and specific IgE to all the nine major food allergens tested in this sample (sesame, peanut, wheat, milk, egg white, soy, walnut, shrimp and cod fish). The estimated heritability of food-specific IgE ranged from 0.15 to 0.35 and was statistically significant for all the nine tested food allergens.
This family-based study demonstrates strong familial aggregation of FA and sensitization to food allergens, especially, among siblings. The heritability estimates indicate that food-specific IgE is likely influenced by both genetic and environmental factors. Together, this study provides strong evidence that both host genetic susceptibility and environmental factors determine the complex trait of IgE-mediated FA.
食物过敏（FA）患病率的不断上升是一个日益严重的临床和公共卫生问题。遗传因素对食物过敏的影响在很大程度上仍不清楚。
本研究调查了食物过敏的家族聚集模式以及遗传因素对食物过敏和食物过敏原致敏的影响程度。
本研究纳入了581个核心家庭（2004名受试者），作为美国伊利诺伊州芝加哥正在进行的食物过敏研究的一部分。食物过敏由一组标准定义，包括发病时间、通过标准化问卷调查获得的临床症状以及通过Phadia ImmunoCAP检测的食物过敏原的确诊特异性IgE临界值，其阳性预测值（PPV）≥95%。使用广义估计方程（GEE）模型研究食物过敏的家族聚集以及对食物过敏原的致敏情况，并对包括年龄、性别、种族和出生顺序等重要协变量进行调整。对食物特异性IgE测量值进行遗传度估计。
先证者儿童的食物过敏是其他兄弟姐妹食物过敏的显著独立预测因素（OR = 2.6，95% CI：1.2 - 5.6，P = 0.01）。在该样本中测试的所有九种主要食物过敏原（芝麻、花生、小麦、牛奶、蛋清、大豆、核桃、虾和鳕鱼）的总IgE和特异性IgE在家庭成员（父亲 - 子女、母亲 - 子女、先证者 - 其他兄弟姐妹）之间存在显著正相关。食物特异性IgE的估计遗传度范围为0.15至0.35，对所有九种测试食物过敏原均具有统计学意义。
这项基于家庭的研究表明食物过敏和对食物过敏原的致敏存在强烈的家族聚集性，尤其是在兄弟姐妹之间。遗传度估计表明食物特异性IgE可能受遗传和环境因素的共同影响。总之，本研究提供了强有力的证据，表明宿主遗传易感性和环境因素共同决定了IgE介导的食物过敏这一复杂性状。
