Association of SLC6A4 methylation with long-term outcomes after stroke: focus on the interaction with suicidal ideation

Hee Ju Kang, Eun Hye Lee, Ju Wan Kim, Sung Wan Kim, Il Seon Shin, Joon Tae Kim, Man Seok Park, Ki Hyun Cho, Jung Soo Han, In Kyoon Lyoo, Jae Min Kim

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9 Scopus citations


Serotonin (5-HT) plays an important role in cerebrovascular homeostasis and psychiatric disorders, including suicidality. Methylation of the serotonin transporter gene (SLC6A4) is associated with 5-HT expression. However, the prognostic roles of SLC6A4 methylation and suicidal ideation (SI) in long-term outcomes of stroke have not been evaluated. We investigated the independent and interactive effects of SLC6A4 methylation and SI immediately after stroke on long-term outcomes. Blood SLC6A4 methylation status and SI based on the suicide item of the Montgomery–Åsberg Depression Rating Scale were assessed in 278 patients at 2 weeks after stroke. After the index stroke, cerebro-cardiovascular events by SLC6A4 methylation status and SI were investigated over an 8–14-year follow-up period and using Cox regression models adjusted for a range of covariates. SLC6A4 hypermethylation and SI within 2 weeks of stroke both predicted worse long-term outcomes, independent of covariates. A significant interaction effect of SI and the methylation status of CpG 4 on long-term stroke outcomes was also identified. The association between SLC6A4 methylation and long-term adverse outcomes may be strengthened in the presence of SI within 2 weeks after stroke. Evaluation of methylation and SI status during the acute phase can be helpful when assessing stroke patients.

Original languageEnglish
Article number2710
JournalScientific Reports
Issue number1
StatePublished - Dec 2021

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