Babushkina Nadezhda P, Bragina Elena Yu, Gomboeva Densema E, Koroleva Iuliia A, Illarioshkin Sergey N, Klyushnikov Sergey A, Abramycheva Nataliya Yu, Nikitina Maria A, Alifirova Valentina M, Litviakov Nikolai V, Ibragimova Marina K, Tsyganov Matvey M, Tsydenova Irina A, Zarubin Aleksei A, Goncharova Irina A, Golubenko Maria V, Salakhov Ramil R, Sleptcov Aleksei A, Kucher Aksana N, Nazarenko Maria S, Puzyrev Valery P
Research Institute of Medical Genetics, Tomsk National Research Medical Center, Russian Academy of Sciences, 10 Ushayka Embankment, Tomsk 634050, Russia.
Research Center of Neurology, 80 Volokolamskoye Shosse, Moscow 125367, Russia.
Epigenomes. 2025 Aug 7;9(3):28. doi: 10.3390/epigenomes9030028.
Studies of comorbid (syntropic) and inversely comorbid (rarely occurring together, i.e., dystropic) diseases have focused on the search for molecular causes of this phenomenon. We investigated DNA methylation levels in regulatory regions of 23 apoptosis-associated genes as candidate loci associated with the "cancer-neurodegeneration" dystropy in patients with Huntington's disease (HD) and patients with non-small cell lung cancer (LC). Statistically significant differences in methylation levels between the HD and LC groups were found for 41 CpG sites in 16 genes. The results show that five genes (, , , , and ) are probably involved in the phenomenon of inverse comorbidity of these diseases. For these genes, the methylation levels of the studied CpG sites were altered in opposite directions in the two groups of patients, compared to the control group. For the gene, the above hypothesis is supported by our analysis of open-access data on gene expression in patients with the aforementioned diagnoses and fits a probable mechanism of the "HD-LC" dystropy.
对共病（同向性）和反向共病（很少同时发生，即异向性）疾病的研究主要集中在寻找这种现象的分子原因。我们研究了23个凋亡相关基因调控区域的DNA甲基化水平，这些区域是与亨廷顿舞蹈症（HD）患者和非小细胞肺癌（LC）患者中“癌症-神经退行性变”异向性相关的候选基因座。在16个基因的41个CpG位点上，发现HD组和LC组之间的甲基化水平存在统计学显著差异。结果表明，五个基因（、、、和）可能与这些疾病的反向共病现象有关。对于这些基因，与对照组相比，两组患者中所研究的CpG位点的甲基化水平呈相反方向改变。对于基因，我们对上述诊断患者的基因表达开放获取数据的分析支持了上述假设，并且符合“HD-LC”异向性的可能机制。
