Allergen sensitization is associated with increased DNA methylation in older men.

Allergen sensitization is associated with increased DNA methylation in older men.
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DOI:
10.1159/000343004
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发表时间:
2013
影响因子:
2.8
通讯作者:
Litonjua AA
Litonjua AA
中科院分区:
医学3区
文献类型:
--
作者:
Sordillo JE;Lange NE;Tarantini L;Bollati V;Zanobetti A;Sparrow D;Vokonas P;Schwartz J;Baccarelli A;Demeo D;Litonjua AA

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由环境暴露或内部生理变化引起的表观遗传修饰的变化可以影响基因表达,并可能最终导致哮喘和过敏等复杂疾病。我们研究了哮喘和过敏表型与逆转录转座子衍生元件DNA甲基化水平的关系。我们使用了来自704名男性(平均年龄73岁)的纵向规范老化研究数据,以评估哮喘、过敏表型和逆转录转座子衍生元件Alu和LINE-1的DNA甲基化水平之间的关系。反转录转座子占基因组的很大一部分(> 30%),并且被高度甲基化以防止表达。使用PCR焦磷酸测序定量外周白色血细胞中Alu和LINE-1元件的甲基化百分比。在DNA甲基化分析前约8年,通过皮肤点刺试验、哮喘和乙酰甲胆碱反应性收集了对常见过敏原致敏的数据。在校正包年、BMI、吸烟、空气污染物、嗜酸性粒细胞百分比、白色血细胞计数和年龄的模型中,既往过敏原致敏与Alu甲基化增加相关(β=0.32 [致敏vs.非致敏],p值0.003)。在接受采访的男性中,5%的受试者报告了哮喘的诊断。Alu和LINE-1甲基化均与哮喘无关。这些数据表明,重复元件的DNA甲基化增加可能与过敏原致敏有关,但似乎与哮喘无关。今后的工作需要确定这些关系的潜在机制。
Variation in epigenetic modifications, arising from either environmental exposures or internal physiological changes, can influence gene expression, and may ultimately contribute to complex diseases such as asthma and allergies. We examined the association of asthma and allergic phenotypes with DNA methylation levels of retrotransposon-derived elements. We used data from 704 men (mean age 73) in the longitudinal Normative Aging Study to assess the relationship between asthma, allergic phenotypes and DNA methylation levels of the retrotransposon derived elements Alu and LINE-1. Retrotransposons represent a large fraction of the genome (> 30%), and are heavily methylated to prevent expression. Percent methylation of Alu and LINE-1 elements in peripheral white blood cells was quantified using PCR pyrosequencing. Data on sensitization to common allergens by skin prick testing, asthma, and methacholine responsiveness was gathered approximately 8 years prior to DNA methylation analysis. Prior allergen sensitization was associated with increased methylation of Alu (β=0.32 [sensitized vs. non-sensitized], p value 0.003), in models adjusted for pack-years, BMI, smoking, air pollutants, percent eosinophils, white blood cell count and age. Of the men interviewed, 5 % of subjects reported diagnosis of asthma. Neither Alu, nor LINE-1 methylation was associated with asthma. These data suggest that increased DNA methylation of repetitive elements may be associated with allergen sensitization, but does not appear to be associated with asthma. Future work is needed to identify potential underlying mechanisms for these relationships.
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