Genetic Variation and Human Diseases Unit, INSERM, U946, Paris, France; Université Paris, France.
J Allergy Clin Immunol. 2012 Jun;129(6):1547-53.e3. doi: 10.1016/j.jaci.2012.04.010.
A previous genome-wide linkage scan in 295 families of the French Epidemiological Study on the Genetics and Environment of Asthma (EGEA) reported strong evidence of linkage of 11p14 to eczema.
Our purpose was to conduct fine-scale mapping of the 11p14 region to identify the genetic variants associated with eczema.
Association analyses were first conducted in the family sample from the French EGEA by using 2 methods: the family-based association method and logistic regression. Replication of the EGEA findings was sought in French Canadian and United Kingdom family samples, which, similarly to EGEA samples, were ascertained through asthma. We also tested for association in 2 German samples ascertained through eczema.
We found significant association of eczema with 11p14 genetic variants in the vicinity of the linkage peak in EGEA (P = 10(-4) for rs1050153 by using the family-based association method, which reached the multiple testing-corrected threshold of 10(-4); P = .003 with logistic regression). Pooled analysis of the 3 asthma-ascertained samples showed strong improvement in the evidence for association (P = 6 × 10(-6) for rs293974, P = 3 × 10(-5) for rs1050153, and P = 8 × 10(-5) for rs15783). No association was observed in the eczema-ascertained samples.
The significant single nucleotide polymorphisms are located within the overlapping anoctamin 3 (ANO3) and mucin 15 (MUC15) genes. Several lines of evidence suggest that MUC15 is a strong candidate for eczema. Further investigation is needed to confirm our findings and to better understand the role of the ANO3/MUC15 locus in eczema and its relationship with respect to asthma.
先前在法国遗传与环境哮喘研究（EGEA）的 295 个家庭的全基因组连锁扫描中报告了 11p14 与湿疹之间存在强烈关联的证据。
我们的目的是对 11p14 区域进行精细作图，以确定与湿疹相关的遗传变异。
首先在法国 EGEA 的家族样本中通过两种方法进行关联分析：基于家庭的关联方法和逻辑回归。通过哮喘来确定的法裔加拿大和英国家族样本中寻求 EGEA 发现的复制。我们还在通过湿疹确定的 2 个德国样本中测试了关联。
我们发现 EGEA 中的连锁峰附近的 11p14 遗传变异与湿疹存在显著关联（使用基于家庭的关联方法时，rs1050153 的 P 值为 10（-4），达到了多重检验校正的阈值 10（-4）；逻辑回归时 P 值为.003）。3 个哮喘确定的样本的合并分析显示关联证据有了很大的改善（rs293974 的 P 值为 6×10（-6），rs1050153 的 P 值为 3×10（-5），rs15783 的 P 值为 8×10（-5））。在湿疹确定的样本中没有观察到关联。
显著的单核苷酸多态性位于重叠的 anoctamin 3（ANO3）和粘蛋白 15（MUC15）基因内。有几条证据表明 MUC15 是湿疹的一个强有力的候选基因。需要进一步的研究来确认我们的发现，并更好地了解 ANO3/MUC15 基因座在湿疹中的作用及其与哮喘的关系。
