INSERM U946, Genetic Variation and Human Diseases Unit, Paris, France; Université Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d'Hématologie, Paris, France.
INSERM U946, Genetic Variation and Human Diseases Unit, Paris, France; Université Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d'Hématologie, Paris, France.
J Allergy Clin Immunol. 2014 Sep;134(3):576-582.e1. doi: 10.1016/j.jaci.2013.12.1074. Epub 2014 Feb 20.
A previous genome-wide linkage scan in 295 families of the French Epidemiological Study on the Genetics and Environment of Asthma (EGEA) showed strong evidence of linkage of the 1p31 region to the combined asthma plus allergic rhinitis (AR) phenotype.
Our purpose was to conduct fine-scale mapping of the 1p31 linkage region to identify the genetic variants associated with asthma plus AR.
Association analyses with the asthma plus rhinitis phenotype were first conducted in the EGEA family sample using the family-based association method (FBAT) and logistic regression. The test of homogeneity of association between asthma plus AR versus asthma alone or AR alone was also applied. Replication of EGEA findings was sought in French-Canadian and United Kingdom family samples.
We found a significant association between asthma plus rhinitis and a 1p31 genetic variant (P = 2 × 10(-5) for rs12122228, which reached the multiple testing-corrected threshold) in EGEA using FBAT. There was evidence of heterogeneity of association between asthma plus AR versus asthma alone or AR alone (P = .03). A Meta-analysis of FBAT results from EGEA and French-Canadian families improved evidence for both association and heterogeneity (P = 5 × 10(-6) and P = .008, respectively), whereas a meta-analysis of EGEA, French-Canadian, and United Kingdom samples based on logistic regression slightly increased the evidence for heterogeneity.
The single nucleotide polymorphism specifically associated to asthma plus rhinitis is located in the flanking 5' untranslated region of the nuclear factor I/A (NFIA) gene, a strong candidate gene for asthma and AR.
先前在法国遗传与环境哮喘研究（EGEA）的 295 个家族进行的全基因组连锁扫描显示，1p31 区域与哮喘加变应性鼻炎（AR）表型之间存在强烈的连锁证据。
我们的目的是对 1p31 连锁区域进行精细作图，以确定与哮喘加 AR 相关的遗传变异。
首先使用基于家庭的关联方法（FBAT）和逻辑回归，对 EGEA 家族样本中的哮喘加鼻炎表型进行关联分析。还应用了哮喘加 AR 与哮喘或 AR 单独之间关联的同质性检验。寻求在法裔加拿大和英国家族样本中复制 EGEA 的发现。
我们使用 FBAT 在 EGEA 中发现哮喘加鼻炎与 1p31 遗传变异之间存在显著关联（rs12122228 的 P = 2 × 10(-5)，达到了多重检验校正的阈值）。哮喘加 AR 与哮喘或 AR 单独之间的关联存在异质性证据（P =.03）。EGEA 和法裔加拿大家族的 FBAT 结果的 Meta 分析改善了关联和异质性的证据（P = 5 × 10(-6)和 P =.008，分别），而基于逻辑回归的 EGEA、法裔加拿大和英国样本的 Meta 分析则略微增加了异质性的证据。
与哮喘加鼻炎特异性相关的单核苷酸多态性位于核因子 I/A（NFIA）基因的侧翼 5'非翻译区，该基因是哮喘和 AR 的一个强有力的候选基因。
