Institute of Research and Development, Duy Tan University, Da Nang, 550000, Viet Nam.
Department of Immunology, Ophthalmology and ENT, School of Medicine, Complutense University, Madrid, Spain.
J Mol Neurosci. 2020 Nov;70(11):1880-1886. doi: 10.1007/s12031-020-01584-x. Epub 2020 May 21.
Suicidal behavior as a psychological problem with high public health burden is associated with a number of genetically determined risk factors. In the current study, we investigated the association between two polymorphisms within the NINJ2 gene and risk of suicide in an Iranian population. The study included 295 individuals who attempted suicide with soft suicide methods, 234 suicide victims and 410 normal controls. The rs11833579 SNP was associated with death from suicide in a codominant model in that the AG genotype decreased the risk of death from suicide compared with the GG genotype (OR (95% CI) = 0.49 (0.34-0.71), adjusted P value = 4e-04). This SNP was also associated with death from suicide in dominant (AG + AA versus GG: OR (95% CI) = 0.63 (0.46-0.87), adjusted P value = 0.011) and overdominant (AG versus GG + AA: OR (95% CI) = 0.49 (0.35-0.69), adjusted P value < 0.0001) models. In addition, this SNP was associated with soft suicide attempts in a codominant model (AG versus AA + GG: OR (95% CI) = 0.7 (0.5-0.98), adjusted P value = 0.02). The rs3806263 SNP was associated with death from suicide in allelic (A versus G: OR (95% CI) = 1.48 (1.17-1.88), adjusted P value = 0.002), codominant (AA versus GG: OR (95% CI) = 3.14 (1.89-5.21), adjusted P value < 0.0001), recessive (AA versus GG + AG: OR (95% CI) = 3.47 (2.15-5.61), adjusted P value < 0.0001), overdominant (AG versus AA + GG: OR (95% CI) = 0.62 (0.45-0.87), adjusted P value = 0.0092) and log-additive models (OR (95% CI) = 1.45 (1.15-1.83), adjusted P value = 0.0034). When comparing allele/genotype frequencies of this SNP between suicide victims and soft suicide attempters, significant associations were found in allelic, codominant, recessive and log-additive models. The AG haplotype (rs11833579 and rs3806263, respectively) was significantly less prevalent among suicide victims compared with controls (OR (95% CI) = 0.37 (0.26-0.52), adjusted P value < 0.0001). This haplotype was also less prevalent among suicide victims vs. soft suicide attempters (OR (95% CI) = 0.43 (0.31-0.61), adjusted P value < 0.0001). The GA haplotype (rs11833579 and rs3806263, respectively) was less frequent among suicide victims compared with controls (OR (95% CI) = 0.63 (0.45-0.89), adjusted P value = 0.0156). Finally, the AA haplotype was more prevalent among suicide victims compared with both controls (OR (95% CI) = 2.37 (1.56-3.6), adjusted P value = 0.0002) and soft suicide attempters (OR (95% CI) = 1.92 (1.32-2.78), adjusted P value = 0.0012). Thus, these two SNPs might be regarded as genetic determinants of suicide risk in Iranian populations. Further studies in different populations are needed to verify these results.
自杀行为是一种具有高公共卫生负担的心理问题,与许多遗传决定的风险因素有关。在当前的研究中,我们调查了 NINJ2 基因内的两个多态性与伊朗人群自杀风险的关系。该研究包括 295 名使用软性自杀方法自杀的个体、234 名自杀死亡者和 410 名正常对照。rs11833579 SNP 与自杀死亡的共显性模型相关,即 AG 基因型与 GG 基因型相比降低了自杀死亡的风险(OR(95%CI)=0.49(0.34-0.71),调整后的 P 值=4e-04)。该 SNP 还与显性(AG+AA 与 GG:OR(95%CI)=0.63(0.46-0.87),调整后的 P 值=0.011)和超显性(AG 与 GG+AA:OR(95%CI)=0.49(0.35-0.69),调整后的 P 值<0.0001)模型中的自杀死亡相关。此外,该 SNP 与共显性模型中的软性自杀企图相关(AG 与 AA+GG:OR(95%CI)=0.7(0.5-0.98),调整后的 P 值=0.02)。rs3806263 SNP 与自杀死亡的等位基因(A 与 G:OR(95%CI)=1.48(1.17-1.88),调整后的 P 值=0.002)、共显性(AA 与 GG:OR(95%CI)=3.14(1.89-5.21),调整后的 P 值<0.0001)、隐性(AA 与 GG+AG:OR(95%CI)=3.47(2.15-5.61),调整后的 P 值<0.0001)、超显性(AG 与 AA+GG:OR(95%CI)=0.62(0.45-0.87),调整后的 P 值=0.0092)和对数相加模型(OR(95%CI)=1.45(1.15-1.83),调整后的 P 值=0.0034)中与自杀死亡相关。在比较自杀死亡者和软性自杀企图者之间该 SNP 的等位基因/基因型频率时,在等位基因、共显性、隐性和对数相加模型中发现了显著的关联。与对照组相比,AG 单倍型(rs11833579 和 rs3806263,分别)在自杀死亡者中明显较少(OR(95%CI)=0.37(0.26-0.52),调整后的 P 值<0.0001)。该单倍型在自杀死亡者与软性自杀企图者之间也较少(OR(95%CI)=0.43(0.31-0.61),调整后的 P 值<0.0001)。与对照组相比,GA 单倍型(rs11833579 和 rs3806263,分别)在自杀死亡者中较少(OR(95%CI)=0.63(0.45-0.89),调整后的 P 值=0.0156)。最后,与对照组(OR(95%CI)=2.37(1.56-3.6),调整后的 P 值=0.0002)和软性自杀企图者(OR(95%CI)=1.92(1.32-2.78),调整后的 P 值=0.0012)相比,AA 单倍型在自杀死亡者中更为常见。因此,这两个 SNP 可能被视为伊朗人群自杀风险的遗传决定因素。需要在不同人群中进行进一步的研究来验证这些结果。