Hearn Nerissa L, Chiu Christine L, Lind Joanne M
Western Sydney University, School of Medicine, Sydney, Australia.
Macquarie University, Faculty of Medicine and Health Sciences, Sydney, Australia.
BMC Med Genomics. 2020 Feb 3;13(1):16. doi: 10.1186/s12920-020-0670-9.
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.
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.
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.
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.
乳糜泻（CD）是一种自身免疫性疾病，其特征是小肠黏膜因膳食麸质而发生炎症。遗传因素在CD中起关键作用，CD患者携带HLA - DQ2或HLA - DQ8单倍型，然而这些单倍型在一半的普通人群中存在，这使得它们成为引发CD的必要但不充分条件。表观遗传修饰，包括可因环境暴露而改变的DNA甲基化，可能有助于解释基因与环境因素之间的相互作用如何共同触发疾病发展。识别CD患者DNA甲基化谱的变化有助于发现参与CD发病和发展的新基因组区域。
使用Illumina InfiniumMethylation450 Beadchip芯片阵列（HM450）比较CD患者和非CD患者唾液中的DNA甲基化谱。将至少在2年前被诊断出患有CD、正在接受无麸质饮食（GFD）且目前无症状的患者与年龄和性别匹配的非CD健康对照进行比较。使用亚硫酸氢盐焦磷酸测序法验证发现存在差异甲基化的区域。这些区域也在另一组更大的CD患者和非CD患者队列中进行了验证。
在HM450上鉴定出HLA - DQB1基因所在的HLA区域内的甲基化差异，但焦磷酸测序无法证实。在最初的试点队列中，焦磷酸测序证实了SLC17A3基因附近存在显著的甲基化差异。有趣的是，在另一组CD患者和非CD患者对照中对相同位点进行焦磷酸测序时，产生了相反方向的显著甲基化差异。
CD患者唾液中似乎存在DNA甲基化谱改变。需要进一步研究以确认这些差异是否真的与CD相关。
