Epigenome-Wide Association Study Indicates Hypomethylation of MTRNR2L8 in Large-Artery Atherosclerosis Stroke.
Shen. Yupei Y; Peng. Chen C; Bai. Qingke Q; Ding. Ying Y; Yi. Xin X; Du. Huihui H; He. Lin L; Zhou. Daizhan D; Chen. Xu X
Key Findings
- Large-artery atherosclerotic stroke patients show over a thousand DNA methylation differences compared to controls
- The promoter region of the humanin gene MTRNR2L8 is significantly hypomethylated (‑13%) in stroke patients
- A diagnostic model using MTRNR2L8 methylation levels can predict stroke with an AUC of 0.774
Practical Outcomes
- For now, there’s no ready‑to‑use protocol—testing DNA methylation isn’t practical for most people. However, the link hints that boosting humanin activity might someday help stroke prevention, so keep an eye on future supplement or lifestyle studies targeting this pathway.
Summary
A study looked at DNA changes in people who had a certain type of stroke and found that a gene called MTRNR2L8, which makes the peptide humanin, is less methylated (a chemical tag) in these patients. This suggests the gene might be more active and could be linked to stroke risk, but the research is still early and doesn’t give direct advice on taking humanin or changing habits.
Abstract
Background and Purpose- Ischemic stroke, a complex and heterogeneous disease, is the second leading cause of death worldwide. Genetic factors and epigenetic modification contribute to the pathogenesis of this disease. However, the effects of epigenetic factors on this disease have not been systematically investigated. Our study was designed to identify methylation alterations in large-artery atherosclerotic stroke. Methods- We conducted an epigenome-wide association analysis of large-artery atherosclerotic stroke using an Infinium HumanMethylation450 array (cases:controls=12:12), and the differentially methylated loci were validated in 2 cohorts (cases:controls, 110:122 and 191:191, respectively) using a Sequenom EpiTYPER assay. Results- In the screening stage, 1012 differentially methylated CpG sites annotated in 672 genes were found to be significantly associated with large-artery atherosclerotic stroke (mean methylation difference >5%, P<0.01). Disease, Gene Ontology, and pathway analysis highlighted the enrichment of these differentially methylated genes in cardiovascular, metabolic, neurological and immune-related functional gene clusters ( P<0.05). We identified a differentially methylated region in the promoter of a humanin gene ( MTRNR2L8, mean methylation difference=-13.01%, P=8.86×10<sup>-14</sup>). We constructed a diagnostic prediction model that was based on the mean number of significantly changed CpG loci in MTRNR2L8 and showed high diagnostic specificity and sensitivity ( P<0.0001, area under the curve=0.774). Conclusions- Together, these findings demonstrate that DNA methylation plays an important role in large-artery atherosclerotic stroke and that methylation of MTRNR2L8 is a potential therapeutic target and diagnostic biomarker for stroke.
Study Information
pubmed
2019
2019-05-14T00:00:00.000Z
10.1161/strokeaha.118.023436