Laboratory for Molecular Neuropsychiatry, Division of Molecular Medicine, Rudjer Boskovic Institute, Zagreb, Croatia.
Genes Brain Behav. 2011 Jul;10(5):565-9. doi: 10.1111/j.1601-183X.2011.00695.x. Epub 2011 May 3.
One of the candidate genes for suicide is also a gene in the pathway for catecholamine degradation encoding an enzyme catechol-O-methyl-transferase (COMT). It harbors a common functional polymorphism, a G to A nucleotide transition resulting in amino acid substitution from valine (Val) to methionine (Met) at position 158 (COMT Val(108/158) Met; rs4680), that has been associated with psychiatric disorders characterized with an increased risk of suicidal behavior. We have performed the first study on Caucasian population examining the association between completed suicide and the COMT Val(108/158) Met polymorphism. The study population consisted of 356 suicide victims and 198 control subjects. Significant difference in COMT Val(108/158) Met variants' (genotypes, alleles and Val carriers) distribution was found only in male groups, between controls and suicide victims (P = 0.018, P = 0.031, P = 0.005), and between controls and violent suicide victims (P = 0.026, P = 0.042, P = 0.010). The r value from the standardized residuals showed that the Met/Met genotype (r = 2.03) in the control group contributed to these significant differences. In contrast to male subjects, no significant differences in the frequency of the COMT Val(108/158) Met variants were detected between female control and female suicide groups; however, the power of calculation (range 0.161-0.680) was below the desired 0.800. In addition, the logistic regression analysis confirmed these significant differences. In conclusion, our results showed the overpresentation of the Met/Met genotype in male control subjects compared with male suicide victims, suggesting that this genotype of the COMT Val(108/158) Met might be a protective factor against suicide.
自杀的候选基因之一也是儿茶酚胺降解途径中的基因,编码儿茶酚-O-甲基转移酶(COMT)。它含有一个常见的功能多态性,即核苷酸从鸟嘌呤(G)到腺嘌呤(A)的转换,导致第 158 位氨基酸从缬氨酸(Val)变为蛋氨酸(Met)(COMT Val(108/158)Met;rs4680),这与具有自杀行为风险增加的精神障碍有关。我们对高加索人群进行了第一项研究,研究了 COMT Val(108/158)Met 多态性与完成自杀之间的关系。研究人群包括 356 名自杀受害者和 198 名对照。仅在男性组中发现 COMT Val(108/158)Met 变体(基因型、等位基因和 Val 携带者)的分布存在显著差异,在对照组和自杀受害者之间(P = 0.018,P = 0.031,P = 0.005),在对照组和暴力自杀受害者之间(P = 0.026,P = 0.042,P = 0.010)。标准化残差的 r 值表明,对照组中 Met/Met 基因型(r = 2.03)导致了这些显著差异。与男性受试者相比,在女性对照组和女性自杀组之间未检测到 COMT Val(108/158)Met 变体的频率存在显著差异;然而,计算能力(范围 0.161-0.680)低于所需的 0.800。此外,逻辑回归分析证实了这些显著差异。总之,我们的结果表明,与男性自杀受害者相比,男性对照组中 Met/Met 基因型的表现更为突出,表明 COMT Val(108/158)Met 的这种基因型可能是自杀的保护因素。