BACKGROUND Coeliac disease (CD) is a autoimmune disease characterised by mucosal inflammation in the small intestine in response to dietary gluten. Genetic factors play a key role with CD individuals carrying either the HLA-DQ2 or HLA-DQ8 haplotype, however these haplotypes are present in half the general population making them necessary but insufficient to cause CD. Epigenetic modifications, including DNA methylation that can change in response to environmental exposure could help to explain how interactions between genes and environmental factors combine to trigger disease development. Identifying changes in DNA methylation profiles in individuals with CD could help discover novel genomic regions involved in the onset and development of CD. METHODS The Illumina InfiniumMethylation450 Beadchip array (HM450) was used to compare DNA methylation profiles in saliva, in CD and non-CD affected individuals. CD individuals who had been diagnosed at least 2 years previously; were on a GFD; and who were currently asymptomatic; were compared to age and sex-matched non-CD affected healthy controls. Bisulphite pyrosequencing was used to validate regions found to be differentially methylated. These regions were also validated in a second larger cohort of CD and non-CD affected individuals. RESULTS Methylation differences within the HLA region at HLA-DQB1 were identified on HM450 but could not be confirmed with pyrosequencing. Significant methylation differences near the SLC17A3 gene were confirmed on pyrosequencing in the initial pilot cohort. Interestingly pyrosequencing sequencing of these same sites within a second cohort of CD and non-CD affected controls produced significant methylation differences in the opposite direction. CONCLUSION Altered DNA methylation profiles appear to be present in saliva in CD individuals. Further work to confirm whether these differences are truly associated with CD is needed.

中文翻译：

---

乳糜泻和非乳糜泻患者唾液 DNA 甲基化谱的比较。


背景技术乳糜泻(CD)是一种自身免疫性疾病，其特征在于响应于膳食麸质的小肠粘膜炎症。遗传因素对于携带 HLA-DQ2 或 HLA-DQ8 单倍型的 CD 个体起着关键作用，然而这些单倍型存在于一般人群的一半中，这使得它们对于引起 CD 是必需的，但不足以引起 CD。表观遗传修饰，包括可因环境暴露而发生变化的 DNA 甲基化，可能有助于解释基因和环境因素之间的相互作用如何结合起来引发疾病的发展。识别 CD 患者 DNA 甲基化谱的变化有助于发现与 CD 发病和发展有关的新基因组区域。方法 使用 Illumina InfiniumMmethylation450 Beadchip 阵列 (HM450) 比较 CD 和非 CD 患者唾液中的 DNA 甲基化谱。至少 2 年前被诊断为 CD 的个体；正在接受 GFD；目前无症状的人；与年龄和性别匹配的非 CD 影响的健康对照进行比较。使用亚硫酸氢盐焦磷酸测序来验证发现差异甲基化的区域。这些区域也在第二个更大的 CD 和非 CD 受影响个体队列中得到了验证。结果 在 HM450 上鉴定出 HLA 区域内 HLA-DQB1 的甲基化差异，但无法通过焦磷酸测序证实。在最初的试点队列中，焦磷酸测序证实了 SLC17A3 基因附近的显着甲基化差异。有趣的是，对第二组 CD 和非 CD 影响的对照中这些相同位点的焦磷酸测序产生了相反方向的显着甲基化差异。 结论 CD 个体的唾液中似乎存在改变的 DNA 甲基化谱。需要进一步的工作来确认这些差异是否真正与 CD 相关。