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Association between a functional polymorphism in the renin-angiotensin system and completed suicide
A Hishimoto1, O Shirakawa, N Nishiguchi
1Division of Psychiatry and Neurology, Department of Environmental Health and Safety, Faculty of Medical Science, Kobe University Graduate School of Medicine, Kobe, Japan.
Summary
Genetic variations in the renin-angiotensin system (RAS) may influence suicide risk. Specifically, the angiotensin-converting enzyme (ACE) I allele is more common in individuals who completed suicide, particularly males.
Area of Science:
- Genetics and Psychiatry
- Neurobiology of Stress Response
- Cardiovascular and Metabolic Genetics
Background:
- Suicide is potentially linked to disruptions in the stress response system and genetic factors.
- The renin-angiotensin system (RAS) plays a role in regulating the stress response.
- Functional polymorphisms in RAS-related genes may alter protein function, impacting biological pathways.
Purpose of the Study:
- To investigate the hypothesis that renin-angiotensin system (RAS) dysregulation is implicated in suicide.
- To examine the association between completed suicides and specific functional polymorphisms in RAS-related genes.
Main Methods:
- Genotyping was performed for four functional polymorphisms in RAS-related genes: angiotensinogen M235T, angiotensin-converting enzyme (ACE) I/D, angiotensin type-1 receptor A1166C, and G-protein-beta3 C825T.
- Case-control study comparing allele frequencies in individuals who completed suicide with those in control groups.
- Statistical analysis to determine the association between specific polymorphisms and suicide completion, with subgroup analysis for sex.
Main Results:
- The 'I' allele of the angiotensin-converting enzyme (ACE) I/D polymorphism was significantly more frequent in completed suicides compared to controls (P = 0.014).
- This association was particularly pronounced in males, with the ACE 'I' allele being more frequent in male completed suicides than in male controls (P = 0.022).
- No significant association was observed between the ACE I/D polymorphism and suicide in females.
Conclusions:
- Genetic alterations in the renin-angiotensin system (RAS), specifically the ACE I/D polymorphism, may contribute to suicide susceptibility.
- The findings suggest a potential role for RAS genetic variations in the predisposition to suicide, particularly in males.
- Further research is warranted to elucidate the precise mechanisms linking RAS gene polymorphisms to suicide pathophysiology.
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