Association between ACE gene polymorphisms and risk of suicide

Abstract

Suicide is a health problem associated with a number of genetic factors. Genetics polymorphisms in several signaling pathways have been shown in the pathophysiology of suicidal behavior. Variants of the angiotensin converting enzyme (ACE) have been demonstrated to affect risk of some neuropsychiatric conditions and suicide attempt. In the current study, we assessed association between ACE rs4646994, rs1799752 and rs4359 polymorphisms and risk of suicide behavior in a population of Iranian patients attempted suicide (320 individuals who attempted suicide with soft methods and 230 suicide victims) and 300 healthy controls. Polymorphisms were genotyped using tetra-ARMS-PCR method. Data was analyzed using SPSS v.22.0. The rs4359 was associated with successful suicide under co-dominant model in a way that TC genotype was identified as a risk genotype (OR (95% CI)= 1.86 (1.26–2.75), P value=-0.02). In dominant model, TT+TC genotypes were associated with higher risk of successful suicide in comparison with CC genotype (OR (95% CI)= 1.71 (1.18–2.47), P value=-0.04). In over-dominant model, TT+CC genotypes were associated with lower risk in comparison with TC genotype (OR (95% CI)= 0.58 (0.41–0.83), P value=-0.03). rs1799752 was associated with higher risk of successful suicide under co-dominant, recessive and over-dominant models. In co-dominant model, while ID genotype increased the risk (OR (95% CI)= 2 (1.37–2.99), P value=0.003), II genotype decreased the risk (OR (95% CI)= 0.2 (0.09–0.45), P value<0.0001) in comparison with DD genotype). In recessive model, II genotype was associated with lower risk in comparison with total sum of the other genotypes (OR (95% CI)= 0.14 (0.07–0.28), P value<0.0001). The rs4646994 was not associated with risk of successful suicide. Besides, rs4359 was associated with risk of suicide attempt under over-dominant model in a way that TT+CC genotypes decreased risk of suicide attempt (OR (95% CI)= 0.67 (0.48–0.93), P value=0.04). rs1799752 was associated with risk of suicide attempt under co-dominant and recessive models in a way that II genotype conferred lower risk of suicide attempt (OR (95% CI)= 0.53 (0.34–0.83), P value=0.03). Finally, rs4646994 was associated with risk of suicide attempt in all models except for recessive model. I allele of this SNP increased risk of suicide attempt (OR (95% CI)= 1.47 (1.15–1.88), P value=0.018). Taken together, ACE1 gene can be considered as a risk locus for suicide behavior among Iranians.