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

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 lon...

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Published in:Scientific reports 2021-02, Vol.11 (1), p.2710-2710, Article 2710
Main Authors: Kang, Hee-Ju, Lee, Eun-Hye, Kim, Ju-Wan, Kim, Sung-Wan, Shin, Il-Seon, Kim, Joon-Tae, Park, Man-Seok, Cho, Ki-Hyun, Han, Jung-Soo, Lyoo, In Kyoon, Kim, Jae-Min
Format: Article
Language:English
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692/53/2422
692/617/375/1370/534
CpG islands
DNA methylation
Homeostasis
Humanities and Social Sciences
Mental disorders
Methylation
multidisciplinary
Regression analysis
Science
Science (multidisciplinary)
Serotonin
Serotonin transporter
Stroke
Suicidal ideation
Suicide
Suicides & suicide attempts
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Summary: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-021-81854-9