Khoo Siew-Kim, Mäkelä Mika, Chandler David, Schultz En Nee, Jamieson Sarra E, Goldblatt Jack, Haahtela Tari, LeSouëf Peter, Zhang Guicheng
School of Paediatrics and Child Health, The University of Western Australia, Perth, WA, Australia.
Skin and Allergy Hospital, Helsinki University Central Hospital, Helsinki, Finland.
Pediatr Allergy Immunol. 2016 Nov;27(7):721-727. doi: 10.1111/pai.12612. Epub 2016 Sep 12.
Finnish and Russian Karelian children have a highly contrasting occurrence of asthma and allergy. In these two environments, we studied associations between total serum immunoglobulin E (IgE) with methylation levels in cluster of differentiation 14 (CD14).
Five hundred Finnish and Russian Karelian children were included in four groups: Finnish children with high IgE (n = 126) and low IgE (n = 124) as well as Russian children with high IgE (n = 125) and low IgE (n = 125). DNA was extracted from whole blood cells and pyrosequenced. Three CpG sites were selected in the promoter region of CD14.
Methylation levels in two of the three CpG sites were higher in the Finnish compared to Russian Karelian children. In the promoter area of CD14, the Finnish compared to Russian children with low IgE had a significant (p < 0.0001) increase in methylation levels at the Amp5Site 2. Likewise, the Finnish compared to Russian children with high IgE had a significant (p = 0.003) increase in methylation levels at the Amp5Site 3. In Russian children with low vs. high IgE, there were significant differences in methylation levels, but this was not the case on the Finnish side. In the regression analysis, adding the methylation variation of CD14 to the model did not explain the higher asthma and allergy risk in the Finnish children.
The methylation levels in the promoter region of CD14 gene were higher in the Finnish compared to Russian Karelian children. However, the methylation variation of this candidate gene did not explain the asthma and allergy contrast between these two areas.
芬兰和俄罗斯卡累利阿儿童的哮喘和过敏发生率存在显著差异。在这两种环境中,我们研究了血清总免疫球蛋白E(IgE)与分化簇14(CD14)甲基化水平之间的关联。
500名芬兰和俄罗斯卡累利阿儿童被纳入四组:高IgE芬兰儿童(n = 126)、低IgE芬兰儿童(n = 124)、高IgE俄罗斯儿童(n = 125)和低IgE俄罗斯儿童(n = 125)。从全血细胞中提取DNA并进行焦磷酸测序。在CD14启动子区域选择了三个CpG位点。
与俄罗斯卡累利阿儿童相比,芬兰儿童中三个CpG位点中的两个位点的甲基化水平更高。在CD14启动子区域,与低IgE俄罗斯儿童相比,低IgE芬兰儿童在Amp5位点2的甲基化水平显著升高(p < 0.0001)。同样,与高IgE俄罗斯儿童相比,高IgE芬兰儿童在Amp5位点3的甲基化水平显著升高(p = 0.003)。在俄罗斯儿童中,低IgE与高IgE儿童的甲基化水平存在显著差异,但在芬兰儿童中并非如此。在回归分析中,将CD14的甲基化变异添加到模型中并不能解释芬兰儿童较高的哮喘和过敏风险。
与俄罗斯卡累利阿儿童相比,芬兰儿童CD14基因启动子区域的甲基化水平更高。然而,该候选基因的甲基化变异并不能解释这两个地区之间哮喘和过敏的差异。