Rigoli L, Salpietro D C, Lavalle R, Cafiero G, Zuccarello D, Barberi I
Department of Pediatrics, University of Messina, School of Medicine, Italy.
Acta Paediatr. 2000 Sep;89(9):1056-61. doi: 10.1080/713794577.
In our study, the genetic linkage of the Fcepsilon RIbeta gene with atopy in 77 affected sibling pairs recruited from an Italian panel of 201 subjects has been examined. Atopy was defined by the presence of a positive skin prick test to one or more common aeroallergens, a positive RAST test to one or more common aeroallergens and an elevated circulating total IgE. Genotype analysis was performed by PCR amplification of Fcepsilon RIbeta CA and CI11-319 CA microsatellites. All the family members were also tested for the Ilepsilon 181 mutation with the ARMS method and for Leu181/Leu183 polymorphism. Seventy-two point five percent (72.5%) of the affected sibling pairs shared their maternal allele and 27.5% did not. Therefore, an increased maternal allele sharing was observed: chi2 = 8.10, p < 0.01. Comparing paternal versus maternal allele sharing, a significant difference was observed for the C1II-319 CA marker (chi2 = 4.32, p < 0.05). Atopy phenotype with positive skin prick test, RASTs, and high total serum IgE also showed greater sharing of maternal than paternal alleles in affected sibling pairs. Of the 201 subjects studied, 17 (8.4%) were positive for Leu181. Ten of these were children and seven (70%) had inherited the variant maternally. The seven children had maternally inherited Leu181/Leu183 and were atopic. Within this sample the maternal inheritance of Fcepsilon RIbeta Leu181/Leu183 was associated with an increased risk of IgE responses to common allergens, raised eosinophil counts and increased skin prick test reactions. Therefore, the variant identified a genetic risk factor for atopy.
The central role of Fcepsilon RIbeta in atopy and the linkage data presented here point to the possibility that genetic variation in Fcepsilon RIbeta or its controlling element may cause differences in the extent of IgE responses between atopic and non-atopic subjects. A search for such mutations or polymorphisms will need to take into account some carriers of atopy among the normal population and genetic heterogeneity among atopic individuals.
在我们的研究中，对从一个由201名受试者组成的意大利样本中招募的77对患病同胞对的Fcepsilon RIbeta基因与特应性进行了遗传连锁分析。特应性的定义为对一种或多种常见气传变应原皮肤点刺试验阳性、对一种或多种常见气传变应原RAST试验阳性以及循环总IgE升高。通过对Fcepsilon RIbeta CA和CI11 - 319 CA微卫星进行PCR扩增来进行基因型分析。所有家庭成员还采用ARMS方法检测了Ilepsilon 181突变以及Leu181/Leu183多态性。72.5%的患病同胞对共享其母系等位基因，27.5%的患病同胞对不共享。因此，观察到母系等位基因共享增加：卡方 = 8.10，p < 0.01。比较父系与母系等位基因共享情况，对于C1II - 319 CA标记观察到显著差异（卡方 = 4.32，p < 0.05）。在患病同胞对中，皮肤点刺试验阳性、RAST试验阳性以及血清总IgE升高的特应性表型也显示母系等位基因共享多于父系等位基因。在所研究的201名受试者中，17名（8.4%）Leu181呈阳性。其中10名是儿童，7名（70%）从母亲那里遗传了该变体。这7名儿童从母亲那里遗传了Leu181/Leu183且患有特应性。在这个样本中，Fcepsilon RIbeta Leu181/Leu183的母系遗传与对常见变应原的IgE反应风险增加、嗜酸性粒细胞计数升高以及皮肤点刺试验反应增强有关。因此，该变体确定了一种特应性的遗传风险因素。
Fcepsilon RIbeta在特应性中的核心作用以及此处呈现的连锁数据表明，Fcepsilon RIbeta或其调控元件的基因变异可能导致特应性和非特应性个体之间IgE反应程度的差异。寻找此类突变或多态性需要考虑正常人群中的一些特应性携带者以及特应性个体之间的遗传异质性。
